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Azbergenov NK, Akhmetova SZ, Nurulla TA, Kaliev AR, Ramankulova AB, Tulyayeva AB, Kereeva NM. Biomarkers used in the diagnosis and prognosis of gastric cancer in young patients: a scientometric analysis. Front Med (Lausanne) 2025; 12:1586742. [PMID: 40270496 PMCID: PMC12014542 DOI: 10.3389/fmed.2025.1586742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Accepted: 03/27/2025] [Indexed: 04/25/2025] Open
Abstract
Introduction Gastric cancer in young people is a global health burden, although it is less common than in other age groups. The use of biomarkers is developing in the diagnosis, treatment selection and prognosis of gastric cancer in young patients. In this bibliometric analysis we aim to evaluate the progress of this knowledge, trend topic development and scientific teams and countries involvements in the topic of biomarkers role in gastric cancer in young patients. Methods The data were obtained from Scopus (536 publications) for the period 1993-2024, all relevant metadata were analyzed using RStudio and Biblioshiny package to perform global trends and hotspots analysis. Results Publication trends show a constant increase in interest in gastric cancer biomarkers used in the diagnosis and prognosis of gastric cancer in young patients (7.71% per year). The leading countries were China, USA, and Japan, between which there is strong and sustained collaborations. International co-authorship is relatively low (19.4%). The most prolific research centers were Sungkyunkwan University, Sun Yat-sen University, and Fudan University. The most productive researchers were Zhang X., Wang Y., and Li Y. Keywords analysis showed an increase in mentions of topics related to diagnostics (biomarkers, immunohistochemistry), personalized medicine and prognosis. Conclusion Bibliometric analysis of more than three decades research articles on gastric cancer biomarkers in young patients showed a steady increase, with strong contributions from leading countries and institutions, highlighting the growing focus on diagnostics, personalized medicine, and prognosis.
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Affiliation(s)
- Nurbek Kozhakhmetuly Azbergenov
- Department of Pathological Anatomy and Forensic Medicine, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Saule Zhumabaevna Akhmetova
- Department of Pathological Anatomy and Forensic Medicine, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Talshyn Amirkhanovna Nurulla
- Department of Pathological Anatomy and Forensic Medicine, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Abdiraman Rsalievich Kaliev
- Department of Pathological Anatomy and Forensic Medicine, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Aigul Bulatovna Ramankulova
- Department of Pathological Anatomy and Forensic Medicine, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Anar Balkashevna Tulyayeva
- Department of Oncology, Medical Center of West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Nurgul Meirimovna Kereeva
- Department of Oncology, Medical Center of West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
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Yang X, Zhang J, Wang P, Wang F, Tang X. Deciphering the Role of CD14 in Helicobacter Pylori-associated Gastritis and Gastric Cancer: Combing Bioinformatics Analysis and Experiments. J Cancer 2025; 16:1918-1933. [PMID: 40092684 PMCID: PMC11905408 DOI: 10.7150/jca.106847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 01/30/2025] [Indexed: 03/19/2025] Open
Abstract
Background: Gastric cancer (GC) is the third leading cause of cancer-related death and is associated with high mortality and morbidity. Helicobacter pylori (HP) infection is the most important cause of GC. We aimed to identify the core genes of HP caused GC and further elucidate the underlying mechanisms. Methods: GC and HP associated gastritis (HPAG) gene expression data were sourced from Gene Expression Omnibus. Key genes affecting GC prognosis were identified using Cytoscape software. Patient groups were formed based on key gene expression, and the immune analyses were performed with R. MNU, derived from nitrite by HP, was given to GC mice (240ppm) for histology and fluorescence assays. For in vitro experiments, cells received MNU (20 μM) stimulation for 24 hours. Results: CD14 was the only key gene identified. A total of 412 GC patients were divided into CD14-high and CD14-low groups. The two groups showed significant differences in immune cell populations and immune checkpoints. In particular, there was a notable increase in M2 macrophages in GC patients with high CD14 expression (P <0.001). GC Patients with high CD14 expression exhibited a more pronounced immune response than those with low CD14 expression, and elevated CD14 expression positively correlated with the efficacy of CTLA4 therapy (P <0.05). These results indicated that CD14 expression was strongly correlated with the GC immune response. A noticeable increase in CD14 levels was observed in MNU-induced GC animals, cell models, and GC patients. In addition, the number of M2 macrophages was increased in MNU-induced GC mice. Conclusion: Reducing CD14 expression may increase the survival rate of GC patients through the modulation of immune responses. The complex mechanism of CD14's influence on prognosis deserves further investigation.
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Affiliation(s)
- Xuefei Yang
- Department of Gastroenterology, Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Beijing, China
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiaqi Zhang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Ping Wang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Fengyun Wang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Xudong Tang
- Department of Gastroenterology, Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Beijing, China
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
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Zeng X, Shapaer T, Tian J, Abudoukelimu A, Zhao Z, Shayimu P, Ma B. Identifying a CD8T cell signature in the tumor microenvironment to forecast gastric cancer outcomes from sequencing data. J Gastrointest Oncol 2024; 15:2067-2078. [PMID: 39554559 PMCID: PMC11565103 DOI: 10.21037/jgo-24-603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 10/14/2024] [Indexed: 11/19/2024] Open
Abstract
Background The tumor microenvironment (TME) could be critical in carcinogenesis, immune evasion, and treatment response. TME-related genes are limited in their ability to predict gastric cancer (GC) outcomes. We utilized data from The Cancer Genome Atlas (TCGA) to investigate the functional roles of TME-related genes in GC. Methods We acquired single-cell data, bulk sequencing data, and clinical characteristics of GC patients from the TCGA database. The CD8T cell genes associated with the TME were selected for bioinformatic analysis in GC. Tumor classification of GC was established through consistent cluster analysis. We then evaluated the prognosis and immune cell infiltration in connection with a CD8T cell-related model for GC. Results The single-cell messenger RNA (mRNA) sequencing (scRNA-Seq) dataset of GSE134520 was utilized to investigate the pathogenesis and disease-specific cell types in GC. Interestingly, compared to healthy tissue, the proportions of CD8Tex cells, malignant cells, and gland mucous increased in GC, whereas the proportion of pit mucous decreased in GC. Since CD8Tex cells may play a vital role in pancreatic adenocarcinoma (PAAD), based on the 612 differentially expressed genes (DEGs) involved in CD8Tex cells, TCGA-GC patients were stratified into low- and high-risk groups. The downregulated DEGs in the low-risk G1 group were associated with proteoglycans in cancer, the cGMP-PKG signaling pathway, focal adhesion, and cell adhesion molecules (CAMs), whereas the upregulated DEGs were associated with viral protein interaction with cytokine and cytokine receptors, the tumor necrosis factor (TNF) signaling pathway, the interleukin (IL)-17 signaling pathway, and the chemokine signaling pathway. Combined with univariate Cox analysis, we ultimately identified 23 CD8T cell-related prognostic genes: TCIM, AADAC, SLC2A3, ZNF331, TSC22D3, CMTM3, ZFP36, VIM, CLDND1, GABARAPL1, SOCS3, RGS1, TCEAL9, RGS2, CD59, SPRY1, EMP3, ZEB2, PDE4B, GLIPR1, ERRFI1, and LBH. Using the Cox regression model to prioritize the 23 CD8T cell-related genes, we finally selected 7 genes: CXCR4, AADAC, SLC2A3, CMTM3, RGS2, CD59, and ZEB2. Conclusions CD8T cell-related genes have a strong association with tumor classification and immune response in GC patients. A CD8T cell-related signature demonstrated robust prognostic predictive performance for GC. Our findings may reveal novel insights into the diagnosis and treatment of GC.
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Affiliation(s)
- Xiangyue Zeng
- Gastrointestinal Surgery, Cancer Hospital Affiliated to Xinjiang Medical University, Xinjiang Medical University, Urumqi, China
| | - Tiannake Shapaer
- Gastrointestinal Surgery, Cancer Hospital Affiliated to Xinjiang Medical University, Xinjiang Medical University, Urumqi, China
| | - Jianguo Tian
- General Surgery Department, Emin County People’s Hospital in Tacheng District, Urumqi, China
| | - Abulajiang Abudoukelimu
- Gastrointestinal Surgery, Cancer Hospital Affiliated to Xinjiang Medical University, Xinjiang Medical University, Urumqi, China
| | - Zeliang Zhao
- Gastrointestinal Surgery, Cancer Hospital Affiliated to Xinjiang Medical University, Xinjiang Medical University, Urumqi, China
| | - Paerhati Shayimu
- Gastrointestinal Surgery, Cancer Hospital Affiliated to Xinjiang Medical University, Xinjiang Medical University, Urumqi, China
| | - Binlin Ma
- Department of Breast and Thyroid Surgery, Cancer Hospital Affiliated to Xinjiang Medical University, Xinjiang Medical University, Urumqi, China
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Qian C, Hui J, Peng Z, Sun X, Zhang J. Mucosal microbiota characterization in gastric cancer identifies immune-activated-related transcripts relevant gastric microbiome signatures. Front Immunol 2024; 15:1435334. [PMID: 39376571 PMCID: PMC11456469 DOI: 10.3389/fimmu.2024.1435334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 09/05/2024] [Indexed: 10/09/2024] Open
Abstract
Tumor microenvironment (TME) immune cells and gastric mucosal microbiome constitute two vital elements of tumor tissue. Increasing evidence has elucidated their clinicopathological significance in predicting outcomes and therapeutic efficacy. However, comprehensive characterization of immune cell-associated microbiome signatures in the TME is still in the early stages of development. Here, we characterized the gastric mucosa microbiome and its associations with immune-activated related transcripts (IATs) in 170 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and quantitative reverse transcription-PCR. Microbial diversity and richness were significantly higher in GC tumor tissues than in non-tumor tissues. Differences in microbial composition between the groups were evident, with Firmicutes, Proteobacteria, Bacteroidota, Campilobacterota, Actinobacteria, Fusobacteriota, Verrucomicrobiota, Acidobacteriota, and Cyanobacteria being the dominant phyla in the gastric mucosal microbiota. Microbial interaction network analysis revealed distinctive centralities of oral bacteria (such as Fusobacterium, Porphyromonas, Prevotella, etc.) in both tumor and normal mucosae networks, suggesting their significant influence on GC microbial ecology. Furthermore, we analyzed the expression of IATs (CXCL9, CXCL10, GZMA, GZMB, PRF1, CD8A, IFNG, TBX2, and TNF) and characterized IAT-relevant gastric microbiome signatures in GC patients. Our results showed that the expression of CXCL9, CXCL10, GZMA, GZMB, PRF1 and IFNG was significantly higher in tumor tissues than in adjacent normal tissues in GC patients. Notably, high expression of IATs in tumor tissues was associated with improved survival in GC patients and could serve as a powerful predictor for disease-free survival. Additionally, analysis of IAT levels and mucosal microbiota diversity revealed a correlation between higher IAT expression and increased microbiota richness and evenness in the IATs high group, suggesting potential interactions between mucosal microbiota and tumor immunopathology. Spearman correlation analysis showed positive associations between IAT expression and specific mucosal bacterial species. Notably, Akkermansia muciniphila demonstrated potential involvement in modulating GZMB expression in the GC mucosal microenvironment. These findings underscore the importance of mucosal microbiota alterations in GC and suggest potential therapeutic targets focusing on modulating the tumor microbiota for improved clinical outcomes. The detailed characterization of these elements has profound implications for both treatment and survival prediction in GC. We observed that microbial diversity and richness were significantly higher in GC tumor tissues compared to non-tumor tissues. These differences highlight the unique microbial landscape of GC tumors and suggest that the microbiome could influence tumor development and progression. Importantly, our study demonstrated that high expression levels of IATs in GC tumor tissues were associated with improved patient survival. This suggests that IATs not only reflect immune activation but also serve as valuable biomarkers for predicting disease-free survival. The potential of IATs as predictive markers underscores their utility in guiding therapeutic strategies and personalizing treatment approaches. Moreover, the correlation between higher IAT expression and increased microbiota richness and evenness suggests that a diverse and balanced microbiome may enhance immune responses and contribute to better clinical outcomes. These findings highlight the critical need to consider mucosal microbiota alterations in GC management. Targeting the tumor microbiota could emerge as a promising therapeutic strategy, potentially leading to more effective treatments and improved patient outcomes. Understanding and modulating the microbiome's role in GC opens new avenues for innovative therapeutic interventions and personalized medicine.
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Affiliation(s)
- Chengjia Qian
- Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Jiang Hui
- Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Ziyao Peng
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Xiaoyan Sun
- Department of Nuclear Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Jiali Zhang
- Central Laboratory, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
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Wang SY, Yang XQ, Wang YX, Shen A, Liang CC, Huang RJ, Cheng UH, Jian R, An N, Xiao YL, Wang LS, Zhao Y, Lin C, Wang CP, Yuan ZP, Yuan SQ. Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy. J Transl Med 2024; 104:102090. [PMID: 38830579 DOI: 10.1016/j.labinv.2024.102090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 05/09/2024] [Accepted: 05/28/2024] [Indexed: 06/05/2024] Open
Abstract
Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.
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Affiliation(s)
- Si-Yu Wang
- Department of Oncology, The First People's Hospital of Yibin, Yibin, China
| | - Xian-Qi Yang
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yu-Xin Wang
- Department of Nuclear Medicine, The First Hospital of Jilin University, Changchun, China
| | - Ao Shen
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Cheng-Cai Liang
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Run-Jie Huang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Un Hio Cheng
- Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Rui Jian
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Nan An
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yu-Long Xiao
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Li-Shuai Wang
- Department of Oncology, The First People's Hospital of Yibin, Yibin, China
| | - Yin Zhao
- Department of Oncology, The First People's Hospital of Yibin, Yibin, China
| | - Chuan Lin
- Department of Oncology, The First People's Hospital of Yibin, Yibin, China
| | - Chang-Ping Wang
- Department of Oncology, The First People's Hospital of Yibin, Yibin, China
| | - Zhi-Ping Yuan
- Department of Oncology, The First People's Hospital of Yibin, Yibin, China
| | - Shu-Qiang Yuan
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
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Liu W, Liu Y, Chen S, Hui J, He S. AURKB promotes immunogenicity and immune infiltration in clear cell renal cell carcinoma. Discov Oncol 2024; 15:286. [PMID: 39014265 PMCID: PMC11252114 DOI: 10.1007/s12672-024-01141-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 07/02/2024] [Indexed: 07/18/2024] Open
Abstract
BACKGROUND Chromatin regulators (CRs) are capable of causing epigenetic alterations, which are significant features of cancer. However, the function of CRs in controlling Clear Cell Renal Cell Carcinoma (ccRCC) is not well understood. This research aims to discover a CRs prognostic signature in ccRCC and to elucidate the roles of CRs-related genes in tumor microenvironment (TME). METHODS Expression profiles and relevant clinical annotations were retrieved from the Cancer Genome Atlas (TCGA) and UCSC Xena platform for progression-free survival (PFS) data. The R package "limma" was used to identify differentially expressed CRs. A predictive model based on five CRs was developed using LASSO-Cox analysis. The model's predictive power and applicability were validated using K-M curves, ROC curves, nomograms, comparisons with other models, stratified survival analyses, and validation with the ICGC cohort. GO and GSEA analyses were performed to investigate mechanisms differentiating low and high riskScore groups. Immunogenicity was assessed using Tumor Mutational Burden (TMB), immune cell infiltrations were inferred, and immunotherapy was evaluated using immunophenogram analysis and the expression patterns of human leukocyte antigen (HLA) and checkpoint genes. Differentially expressed CRs (DECRs) between low and high riskScore groups were identified using log2|FC|> 1 and FDR < 0.05. AURKB, one of the high-risk DECRs and a component of our prognostic model, was selected for further analysis. RESULTS We constructed a 5 CRs signature, which demonstrated a strong capacity to predict survival and greater applicability in ccRCC. Elevated immunogenicity and immune infiltration in the high riskScore group were associated with poor prognosis. Immunotherapy was more effective in the high riskScore group, and certain chemotherapy medications, including cisplatin, docetaxel, bleomycin, and axitinib, had lower IC50 values. Our research shows that AURKB is critical for the immunogenicity and immune infiltration of the high riskScore group. CONCLUSION Our study produced a reliable prognostic prediction model using only 5 CRs. We found that AURKB promotes immunogenicity and immune infiltration. This research provides crucial support for the development of prognostic biomarkers and treatment strategies for ccRCC.
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Affiliation(s)
- Weihao Liu
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Ying Liu
- Department of Oncology, Huadu District People's Hospital of Guangzhou, Guangzhou, 510810, Guangdong, China
| | - Shisheng Chen
- Department of Urology, Dongguan Tungwah Hospital, Dongguan, 523110, Guangdong, China
| | - Jialiang Hui
- Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
| | - Shuhua He
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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Wang S, Zhang W, Wu X, Zhu Z, Chen Y, Liu W, Xu J, Chen L, Zhuang C. Comprehensive analysis of T-cell regulatory factors and tumor immune microenvironment in stomach adenocarcinoma. BMC Cancer 2024; 24:570. [PMID: 38714987 PMCID: PMC11077837 DOI: 10.1186/s12885-024-12302-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 04/22/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most prevalent malignant tumors worldwide and is associated with high morbidity and mortality rates. However, the specific biomarkers used to predict the postoperative prognosis of patients with gastric cancer remain unknown. Recent research has shown that the tumor microenvironment (TME) has an increasingly positive effect on anti-tumor activity. This study aims to build signatures to study the effect of certain genes on gastric cancer. METHODS Expression profiles of 37 T cell-related genes and their TME characteristics were comprehensively analyzed. A risk signature was constructed and validated based on the screened T cell-related genes, and the roles of hub genes in GC were experimentally validated. RESULTS A novel T cell-related gene signature was constructed based on CD5, ABCA8, SERPINE2, ESM1, SERPINA5, and NMU. The high-risk group indicated lower overall survival (OS), poorer immune efficacy, and higher drug resistance, with SERPINE2 promoting GC cell proliferation, according to experiments. SERPINE2 and CXCL12 were significantly correlated, indicating poor OS via the Youjiang cohort. CONCLUSIONS This study identified T cell-related genes in patients with stomach adenocarcinoma (STAD) for prognosis estimation and proposed potential immunotherapeutic targets for STAD.
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Affiliation(s)
- Shuchang Wang
- Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Weifeng Zhang
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Xinrui Wu
- Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Zhu Zhu
- Department of Clinical Medicine, Medical School of Nantong University, Nantong, China
| | - Yuanbiao Chen
- Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Wangrui Liu
- Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Junnfei Xu
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
| | - Li Chen
- Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
- Department of Nursing, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
| | - Chun Zhuang
- Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
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Liu R, Liu J, Cao Q, Chu Y, Chi H, Zhang J, Fu J, Zhang T, Fan L, Liang C, Luo X, Yang X, Li B. Identification of crucial genes through WGCNA in the progression of gastric cancer. J Cancer 2024; 15:3284-3296. [PMID: 38817876 PMCID: PMC11134444 DOI: 10.7150/jca.95757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 04/11/2024] [Indexed: 06/01/2024] Open
Abstract
Background: To explore the hub gene closely related to the progression of gastric cancer (GC), so as to provide a theoretical basis for revealing the therapeutic mechanism of GC. Methods: The gene expression profile and clinical data of GSE15459 in Gene Expression Omnibus (GEO) database were downloaded. The weighted gene co-expression network analysis (WGCNA) was used to screen the key modules related to GC progression. Survival analysis was used to assess the influence of hub genes on patients' outcomes. CIBERSORT analysis was used to predict the tissue infiltrating immune cells in patients. Immunohistochemical staining was conducted to further verify the expression of hub genes. Results: Through WGCNA, a total of 26 co-expression modules were constructed, in which salmon module and royalblue module had strong correlation with GC progression. The results of enrichment analysis showed that genes in the two modules were mainly involved in toll-like receptor signaling pathway, cholesterol metabolism and neuroactive ligand-receptor interaction. Six hub genes (C1QA, C1QB, C1QC, FCER1G, FPR3 and TYROBP) related to GC progression were screened. Survival analysis showed overall survival in the high expression group was significantly lower than that in the low expression group. CIBERSORT analysis revealed that immune characteristics difference between patients in early stage and advanced stage. Immunohistochemical results confirmed that C1QB, FCER1G, FPR3 and TYROBP were significantly associated with disease progression in GC. Conclusion: Our study identified that C1QB, FCER1G, FPR3 and TYROBP played important roles in the progression of GC, and their specific mechanisms are worth further study.
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Affiliation(s)
- Rui Liu
- Vascular surgery Department, The Affiliated Hospital of Southwest Medical University, Lu Zhou, China
- Department of gastrointestinal surgery, Meishan People 's Hospital, Meishan, China
| | - Jie Liu
- Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Sichuan, China
- Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Sichuan, China
- Department of general surgery, Dazhou Central Hospital, Dazhou, China
| | - Qiang Cao
- School of Medicine, Macau University of Science and Technology, 999078, Macau, China
| | - Yanpeng Chu
- Department of general surgery, Dazhou Central Hospital, Dazhou, China
- Medical College, Sichuan University of Arts and Science, Dazhou, China
| | - Hao Chi
- Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Sichuan, China
- Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Jun Zhang
- Department of general surgery, Dazhou Central Hospital, Dazhou, China
| | - Jiangping Fu
- Oncology department, Dazhou Central Hospital, Dazhou, China
| | - Tianchi Zhang
- Department of general surgery, Dazhou Central Hospital, Dazhou, China
| | - Linguang Fan
- Department of general surgery, Dazhou Central Hospital, Dazhou, China
| | - Chaozhong Liang
- Department of general surgery, Dazhou Central Hospital, Dazhou, China
| | - Xiufang Luo
- Geriatric department, Dazhou Central Hospital, Dazhou, China
| | - Xiaoli Yang
- Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Sichuan, China
- Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Bo Li
- Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Sichuan, China
- Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Sichuan, China
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Liu SS, Wan QS, Lv C, Wang JK, Jiang S, Cai D, Liu MS, Wang T, Zhang KH. Integrating trans-omics, cellular experiments and clinical validation to identify ILF2 as a diagnostic serum biomarker and therapeutic target in gastric cancer. BMC Cancer 2024; 24:465. [PMID: 38622522 PMCID: PMC11017608 DOI: 10.1186/s12885-024-12175-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 03/24/2024] [Indexed: 04/17/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) lacks serum biomarkers with clinical diagnostic value. Multi-omics analysis is an important approach to discovering cancer biomarkers. This study aimed to identify and validate serum biomarkers for GC diagnosis by cross-analysis of proteomics and transcriptomics datasets. METHODS A cross-omics analysis was performed to identify overlapping differentially expressed genes (DEGs) between our previous aptamer-based GC serum proteomics dataset and the GC tissue RNA-Seq dataset in The Cancer Genome Atlas (TCGA) database, followed by lasso regression and random forest analysis to select key overlapping DEGs as candidate biomarkers for GC. The mRNA levels and diagnostic performance of these candidate biomarkers were analyzed in the original and independent GC datasets to select valuable candidate biomarkers. The valuable candidate biomarkers were subjected to bioinformatics analysis to select those closely associated with the biological behaviors of GC as potential biomarkers. The clinical diagnostic value of the potential biomarkers was validated using serum samples, and their expression levels and functions in GC cells were validated using in vitro cell experiments. RESULTS Four candidate biomarkers (ILF2, PGM2L1, CHD7, and JCHAIN) were selected. Their mRNA levels differed significantly between tumor and normal tissues and showed different diagnostic performances for GC, with areas under the receiver operating characteristic curve (AUROCs) of 0.629-0.950 in the TCGA dataset and 0.736-0.840 in the Gene Expression Omnibus (GEO) dataset. In the bioinformatics analysis, only ILF2 (interleukin enhancer-binding factor 2) gene levels were associated with immune cell infiltration, some checkpoint gene expression, chemotherapy sensitivity, and immunotherapy response. Serum levels of ILF2 were higher in GC patients than in controls, with an AUROC of 0.944 for the diagnosis of GC, and it was also detected in the supernatants of GC cells. Knockdown of ILF2 by siRNA significantly reduced the proliferation and colony formation of GC cells. Overexpression of ILF2 significantly promotes the proliferation and colony formation of gastric cancer cells. CONCLUSIONS Trans-omics analysis of proteomics and transcriptomics is an efficient approach for discovering serum biomarkers, and ILF2 is a potential diagnostic biomarker and therapeutic target of gastric cancer.
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Affiliation(s)
- Shao-Song Liu
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University; Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, China, No 17, Yongwai Zheng Street, 330006, Nanchang, China
| | - Qin-Si Wan
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University; Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, China, No 17, Yongwai Zheng Street, 330006, Nanchang, China
| | - Cong Lv
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University; Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, China, No 17, Yongwai Zheng Street, 330006, Nanchang, China
| | - Jin-Ke Wang
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University; Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, China, No 17, Yongwai Zheng Street, 330006, Nanchang, China
| | - Song Jiang
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University; Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, China, No 17, Yongwai Zheng Street, 330006, Nanchang, China
| | - Dan Cai
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University; Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, China, No 17, Yongwai Zheng Street, 330006, Nanchang, China
| | - Mao-Sheng Liu
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University; Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, China, No 17, Yongwai Zheng Street, 330006, Nanchang, China
| | - Ting Wang
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University; Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, China, No 17, Yongwai Zheng Street, 330006, Nanchang, China
| | - Kun-He Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University; Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, China, No 17, Yongwai Zheng Street, 330006, Nanchang, China.
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10
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Sullivan KM, Li H, Yang A, Zhang Z, Munoz RR, Mahuron KM, Yuan YC, Paz IB, Von Hoff D, Han H, Fong Y, Woo Y. Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer. Int J Mol Sci 2024; 25:4117. [PMID: 38612926 PMCID: PMC11012629 DOI: 10.3390/ijms25074117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/27/2024] [Accepted: 04/05/2024] [Indexed: 04/14/2024] Open
Abstract
A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2TS, MRC1; MS4A4A; CD36; CCL13; CCL18; CCL23; SLC38A6; FGL2; FN1; MAF) and M1 (M1TS, CCR7; IL2RA; CXCL11; CCL19; CXCL10; PLA1A; PTX3) macrophages, and cytolytic T-lymphocytes (CTLTS, GZMA; GZMB; GZMH; GZMM; PRF1). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2TS expression was associated with histological types and later stages. Low M2TS expression was associated with significantly better 5-year OS and DFI. We validated M2TS in prospectively collected peritoneal fluid of a GC patient cohort (n = 28). Single-cell RNA sequencing was used for signature expression in CD68+CD163+ cells and the log-rank test compared OS. GC patients with high M2TS in CD68+CD163+ cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2TS was significantly and independently associated with survival. As an independent predictor of poor survival, M2TS may be prognostic in primary tumors and peritoneal fluid of GC patients.
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Affiliation(s)
- Kevin M. Sullivan
- Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA; (K.M.S.); (A.Y.); (Z.Z.); (K.M.M.); (I.B.P.); (Y.F.)
| | - Haiqing Li
- Integrative Genome Core, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA; (H.L.); (Y.-C.Y.)
- Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA 91010, USA
| | - Annie Yang
- Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA; (K.M.S.); (A.Y.); (Z.Z.); (K.M.M.); (I.B.P.); (Y.F.)
| | - Zhifang Zhang
- Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA; (K.M.S.); (A.Y.); (Z.Z.); (K.M.M.); (I.B.P.); (Y.F.)
| | - Ruben R. Munoz
- Molecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA; (R.R.M.); (D.V.H.); (H.H.)
| | - Kelly M. Mahuron
- Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA; (K.M.S.); (A.Y.); (Z.Z.); (K.M.M.); (I.B.P.); (Y.F.)
| | - Yate-Ching Yuan
- Integrative Genome Core, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA; (H.L.); (Y.-C.Y.)
| | - Isaac Benjamin Paz
- Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA; (K.M.S.); (A.Y.); (Z.Z.); (K.M.M.); (I.B.P.); (Y.F.)
| | - Daniel Von Hoff
- Molecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA; (R.R.M.); (D.V.H.); (H.H.)
| | - Haiyong Han
- Molecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA; (R.R.M.); (D.V.H.); (H.H.)
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA; (K.M.S.); (A.Y.); (Z.Z.); (K.M.M.); (I.B.P.); (Y.F.)
| | - Yanghee Woo
- Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA; (K.M.S.); (A.Y.); (Z.Z.); (K.M.M.); (I.B.P.); (Y.F.)
- Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
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11
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Konstantis G, Tsaousi G, Pourzitaki C, Kasper-Virchow S, Zaun G, Kitsikidou E, Passenberg M, Tseriotis VS, Willuweit K, Schmidt HH, Rashidi-Alavijeh J. Identification of Key Genes Associated with Tumor Microenvironment Infiltration and Survival in Gastric Adenocarcinoma via Bioinformatics Analysis. Cancers (Basel) 2024; 16:1280. [PMID: 38610959 PMCID: PMC11010876 DOI: 10.3390/cancers16071280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 03/21/2024] [Accepted: 03/23/2024] [Indexed: 04/14/2024] Open
Abstract
OBJECTIVE Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development. METHODS We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. RESULTS Cytoscape software facilitated the identification of nine hub DEGs, namely, FN1, COL1A1, COL1A2, THBS2, COL3A1, COL5A1, APOE, SPP1, and BGN. Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes, FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN were found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells. CONCLUSION Our findings suggest that the identified hub genes, particularly BGN, FN1, COL1A2, THBS2, COL3A1, and COL5A1, play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients.
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Affiliation(s)
- Georgios Konstantis
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (C.P.); (V.S.T.)
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, 45141 Essen, Germany
| | - Georgia Tsaousi
- Department of Anesthesiology and ICU, Medical School, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece;
| | - Chryssa Pourzitaki
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (C.P.); (V.S.T.)
| | - Stefan Kasper-Virchow
- Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany
| | - Gregor Zaun
- Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany
| | - Elisavet Kitsikidou
- Department of Internal Medicine, Evangelical Hospital Dusseldorf, 40217 Dusseldorf, Germany;
| | - Moritz Passenberg
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, 45141 Essen, Germany
| | - Vasilis Spyridon Tseriotis
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (C.P.); (V.S.T.)
| | - Katharina Willuweit
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, 45141 Essen, Germany
| | - Hartmut H. Schmidt
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, 45141 Essen, Germany
| | - Jassin Rashidi-Alavijeh
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, 45141 Essen, Germany
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12
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Ma XT, Liu X, Ou K, Yang L. Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer. World J Gastrointest Oncol 2024; 16:919-932. [PMID: 38577455 PMCID: PMC10989356 DOI: 10.4251/wjgo.v16.i3.919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 12/16/2023] [Accepted: 02/02/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND Treatment options for patients with gastric cancer (GC) continue to improve, but the overall prognosis is poor. The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present, and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups. AIM To determined the effects of differentially expressed immune-related genes (DEIRGs) on the development, prognosis, tumor microenvironment (TME), and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations. METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas (TCGA), and immune-related genes (IRGs) were searched from ImmPort. DEIRGs were extracted from the intersection of the differentially-expressed genes (DEGs) and IRGs lists. The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes (KEGGs) and Gene Ontology (GO) databases. To identify genes associated with prognosis, a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression. The tumor risk score was divided into high- and low-risk groups. The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model. The infiltration of immune cells was obtained using 'CIBERSORT,' and the infiltration of immune subgroups in high- and low-risk groups was analyzed. The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed. RESULTS We collected 412 GC and 36 adjacent tissue samples, and identified 3627 DEGs and 1311 IRGs. A total of 482 DEIRGs were obtained. GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes, receptor ligand activity, and signaling receptor activators. KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors, neuroactive ligand receptor interactions, and viral protein interactions. We ultimately obtained an immune-related signature based on 10 genes, including 9 risk genes (LCN1, LEAP2, TMSB15A mRNA, DEFB126, PI15, IGHD3-16, IGLV3-22, CGB5, and GLP2R) and 1 protective gene (LGR6). Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, and risk curves confirmed that the risk model had good predictive ability. Multivariate COX analysis showed that age, stage, and risk score were independent prognostic factors for patients with GC. Meanwhile, patients in the low-risk group had higher tumor mutation burden and immunophenotype, which can be used to predict the immune checkpoint inhibitor response. Both cytotoxic T lymphocyte antigen4+ and programmed death 1+ patients with lower risk scores were more sensitive to immunotherapy. CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME. By providing risk factor analysis and prognostic information, our risk model can provide new directions for immunotherapy in GC patients.
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Affiliation(s)
- Xiao-Ting Ma
- Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiu Liu
- Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Kai Ou
- Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Lin Yang
- Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Liu N, Wu Y, Tao Y, Zheng J, Huang X, Yang L, Zhang X. Differentiation of Hepatocellular Carcinoma from Intrahepatic Cholangiocarcinoma through MRI Radiomics. Cancers (Basel) 2023; 15:5373. [PMID: 38001633 PMCID: PMC10670473 DOI: 10.3390/cancers15225373] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/25/2023] [Accepted: 11/06/2023] [Indexed: 11/26/2023] Open
Abstract
The purpose of this study was to investigate the efficacy of magnetic resonance imaging (MRI) radiomics in differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC). The clinical and MRI data of 129 pathologically confirmed HCC patients and 48 ICC patients treated at the Affiliated Hospital of North Sichuan Medical College between April 2016 and December 2021 were retrospectively analyzed. The patients were randomly divided at a ratio of 7:3 into a training group of 124 patients (90 with HCC and 34 with ICC) and a validation group of 53 patients (39 with HCC and 14 with ICC). Radiomic features were extracted from axial fat suppression T2-weighted imaging (FS-T2WI) and axial arterial-phase (AP) and portal-venous-phase (PVP) dynamic-contrast-enhanced MRI (DCE-MRI) sequences, and the corresponding datasets were generated. The least absolute shrinkage and selection operator (LASSO) method was used to select the best radiomic features. Logistic regression was used to establish radiomic models for each sequence (FS-T2WI, AP and PVP models), a clinical model for optimal clinical variables (C model) and a joint radiomics model (JR model) integrating the radiomics features of all the sequences as well as a radiomics-clinical model combining optimal radiomic features and clinical risk factors (RC model). The performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC). The AUCs of the FS-T2WI, AP, PVP, JR, C and RC models for distinguishing HCC from ICC were 0.693, 0.863, 0.818, 0.914, 0.936 and 0.977 in the training group and 0.690, 0.784, 0.727, 0.802, 0.860 and 0.877 in the validation group, respectively. The results of this study suggest that MRI-based radiomics may help noninvasively differentiate HCC from ICC. The model integrating the radiomics features and clinical risk factors showed a further improvement in performance.
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Affiliation(s)
- Ning Liu
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
- Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region (Hospital. C.T.), Chengdu 610041, China
| | - Yaokun Wu
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Yunyun Tao
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Jing Zheng
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Xiaohua Huang
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Lin Yang
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
| | - Xiaoming Zhang
- Medical Imaging Key Laboratory of Sichuan Province, Interventional Medical Center, Department of Radiology, Medical Research Center, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; (N.L.); (Y.W.); (Y.T.); (J.Z.); (X.H.); (X.Z.)
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Bai Z, Yan C, Chang D. Prediction and therapeutic targeting of the tumor microenvironment-associated gene CTSK in gastric cancer. Discov Oncol 2023; 14:200. [PMID: 37930479 PMCID: PMC10628060 DOI: 10.1007/s12672-023-00821-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 11/02/2023] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND Cathepsin-K (CTSK) is overexpressed in Gastric cancer (GC) and the mechanism of its overexpression in GC is still unclear. The present work found CTSK as a potential predictive biomarker and immunotherapeutic target for GC based on the tumor microenvironment (TME). METHODS From public databases, gene expression profiles and clinical data of GC were downloaded to analyze the distribution of stromal and immune cells and tumor abundance in TME. Differentially expressed genes (DEGs) associated with TME were obtained by differential analysis, followed by cross-screening to obtain CTSK as a gene associated with TME. Next, a series of methods and tools were employed to explore the relationships between clinicopathological features of GC and CTSK expression as well as prognosis, tumor immune microenvironment, immune checkpoints and drug sensitivity. And GSEA was used to investigate the potential role of CTSK in the tumor microenvironment of GC. RESULTS From the dataset, we obtained a total of 656 DEGs associated with TME and the stromal component of TME was found to be closely involved in GC prognosis. CTSK was cross-screened as the key gene associated with TME by the PPI network and univariate Cox regression analysis. Pan-cancer analysis revealed significant high expression of CTSK in a variety of cancers. Subsequently, we hypothesized that high-expressed CTSK was closely correlated with poor prognosis and lymph node metastasis of tumors, and that CTSK, a GC TME-related gene, was largely involved in a range of biological behaviors of tumors, with a significant correlation between several immune cells. CONCLUSION CTSK was validated as a potential prognostic biomarker related to TME of GC and could be a promising next-generation immunotherapeutic target for GC.
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Affiliation(s)
- Zilong Bai
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shanxi, China
| | - Chunyu Yan
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shanxi, China
| | - Dongmin Chang
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shanxi, China.
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Xu JL, Yang MX, Lan HR, Jin KT. Could immunoscore improve the prognostic and therapeutic management in patients with solid tumors? Int Immunopharmacol 2023; 124:110981. [PMID: 37769534 DOI: 10.1016/j.intimp.2023.110981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 09/20/2023] [Accepted: 09/20/2023] [Indexed: 10/03/2023]
Abstract
The Immunoscore (ISc) is an emerging immune-based scoring system that has shown potential in improving the prognostic and therapeutic management of patients with solid tumors. The ISc evaluates the immune infiltrate within the tumor microenvironment (TME) and has demonstrated superior predictive ability compared to traditional histopathological parameters. It has been particularly promising in colorectal, lung, breast, and melanoma cancers. This review summarizes the clinical evidence supporting the prognostic value of the ISc and explores its potential in guiding therapeutic decisions, such as the selection of adjuvant therapies and recognizing patients likely to profit from immune checkpoint inhibitors (ICIs). The challenges and future directions of ISc implementation are also discussed, including standardization and integration into routine clinical practice.
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Affiliation(s)
- Jing-Lun Xu
- Department of Dermatology, Jinhua Fifth Hospital, Jinhua, Zhejiang 321000, China
| | - Meng-Xiang Yang
- Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang 321000, China
| | - Huan-Rong Lan
- Department of Surgical Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, China.
| | - Ke-Tao Jin
- Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang 321000, China.
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16
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Shao Y, Lan Y, Chai X, Gao S, Zheng J, Huang R, Shi Y, Xiang Y, Guo H, Xi Y, Yang L, Yang T. CXCL8 induces M2 macrophage polarization and inhibits CD8 + T cell infiltration to generate an immunosuppressive microenvironment in colorectal cancer. FASEB J 2023; 37:e23173. [PMID: 37665572 DOI: 10.1096/fj.202201982rrr] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 08/02/2023] [Accepted: 08/21/2023] [Indexed: 09/05/2023]
Abstract
The poor prognosis of immunotherapy in patients with colorectal cancer (CRC) necessitates a comprehensive understanding of the immunosuppressive mechanisms within tumor microenvironment (TME). Undoubtedly, the anti-tumor immune cells play an indispensable role in immune tolerance. Therefore, it is imperative to investigate novel immune-related factors that have the capacity to enhance anti-tumor immunity. Here, we employed bioinformatic analysis using R and Cytoscape to identify the hub gene chemokine (C-X-C motif) ligand 8 (CXCL8), which is overexpressed in CRC, in the malignant progression of CRC. However, its specific role of CXCL8 in CRC immunity remains to be elucidated. For this purpose, we evaluated how tumor-derived CXCL8 promotes M2 macrophage infiltration by in vivo and in vitro, which can be triggered by IL-1β within TME. Mechanistically, CXCL8-induced polarization of M2 macrophages depends on the activation of the STAT3 signaling. Finally, immunohistochemistry and multiplexed immunohistochemistry analysis identified that CXCL8 not only enhances PD-L1+ M2 macrophage infiltration but also attenuates the recruitment of PD-1+ CD8+ T cells in murine CRC models. Together, these findings emphasize the critical role for CXCL8 in promoting M2 macrophage polarization and inhibiting CD8+ T cell infiltration, thereby links CXCL8 to the emergency of immunosuppressive microenvironment facilitating tumor evasion. Overall, these findings may provide novel strategy for CRC immunotherapy.
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Affiliation(s)
- Ying Shao
- Department of Pathophysiology, Shanxi Medical University, Taiyuan, China
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China
- Higher Education Key Laboratory of Tumor Immunology & Targeted Drug Development in Shanxi Province, Shanxi Medical University, Taiyuan, China
| | - Yan Lan
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China
- Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China
| | - Xinyue Chai
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China
- Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China
| | - Shuhua Gao
- Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China
| | - Jinxiu Zheng
- Higher Education Key Laboratory of Tumor Immunology & Targeted Drug Development in Shanxi Province, Shanxi Medical University, Taiyuan, China
- Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China
| | - Rui Huang
- Higher Education Key Laboratory of Tumor Immunology & Targeted Drug Development in Shanxi Province, Shanxi Medical University, Taiyuan, China
- Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China
| | - Yu Shi
- Higher Education Key Laboratory of Tumor Immunology & Targeted Drug Development in Shanxi Province, Shanxi Medical University, Taiyuan, China
- Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China
| | - Yi Xiang
- Department of Orthpaedics, The Logistics Support Forces of Chinese PLA 985 Hospital, Taiyuan, China
| | - Hongmei Guo
- Department of Casualty Management, The Logistics Support Forces of Chinese PLA 985 Hospital, Taiyuan, China
| | - Yanfeng Xi
- Department of Pathology, Shanxi Cancer Hospital, Taiyuan, China
| | - Lijun Yang
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China
- Higher Education Key Laboratory of Tumor Immunology & Targeted Drug Development in Shanxi Province, Shanxi Medical University, Taiyuan, China
- Department of Pharmacology, Shanxi Medical University, Taiyuan, China
| | - Tao Yang
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China
- Higher Education Key Laboratory of Tumor Immunology & Targeted Drug Development in Shanxi Province, Shanxi Medical University, Taiyuan, China
- Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China
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17
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Guo Y, Zhang Y, Cen K, Dai Y, Mai Y, Hong K. Construction and validation of a signature for T cell-positive regulators related to tumor microenvironment and heterogeneity of gastric cancer. Front Immunol 2023; 14:1125203. [PMID: 37711621 PMCID: PMC10498473 DOI: 10.3389/fimmu.2023.1125203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 08/07/2023] [Indexed: 09/16/2023] Open
Abstract
Background Positive regulators of T cell function play a vital role in the proliferation and differentiation of T cells. However, their functions in gastric cancer have not been explored so far. Methods The TCGA-STAD dataset was utilized to perform consensus clustering in order to identify subtypes related to T cell-positive regulators. The prognostic differentially expressed genes of these subtypes were identified using the least absolute shrinkage and selection operator (LASSO) regression analysis. To validate the robustness of the identified signature, verification analyses were conducted across the TCGA-train, TCGA-test, and GEO datasets. Additionally, a nomogram was constructed to enhance the clinical efficacy of this predictive tool. Transwell migration, colony formation, and T cell co-culture assays were used to confirm the function of the signature gene in gastric cancer and its influence on T cell activation. Results Two distinct clusters of gastric cancer, related to T cell-positive regulation, were discovered through the analysis of gene expression. These clusters exhibited notable disparities in terms of survival rates (P = 0.028), immune cell infiltration (P< 0.05), and response to immunotherapy (P< 0.05). Furthermore, a 14-gene signature was developed to classify gastric cancer into low- and high-risk groups, revealing significant differences in survival rates, tumor microenvironment, tumor mutation burden, and drug sensitivity (P< 0.05). Lastly, a comprehensive nomogram model was constructed, incorporating risk factors and various clinical characteristics, to provide an optimal predictive tool. Additionally, an assessment was conducted on the purported molecular functionalities of low- and high-risk gastric cancers. Suppression of DNAAF3 has been observed to diminish the migratory and proliferative capabilities of gastric cancer, as well as attenuate the activation of T cells induced by gastric cancer within the tumor microenvironment. Conclusion We identified an ideal prognostic signature based on the positive regulators of T cell function in this study.
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Affiliation(s)
- Yangyang Guo
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Yingjue Zhang
- Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Kenan Cen
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Ying Dai
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Yifeng Mai
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Kai Hong
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
- Medicine School, Ningbo University, Ningbo, Zhejiang, China
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18
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Jia W, Luo Q, Wu J, Shi Y, Guan Q. Neutrophil elastase as a potential biomarker related to the prognosis of gastric cancer and immune cell infiltration in the tumor immune microenvironment. Sci Rep 2023; 13:13447. [PMID: 37596368 PMCID: PMC10439106 DOI: 10.1038/s41598-023-39404-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 07/25/2023] [Indexed: 08/20/2023] Open
Abstract
Exploring biomarkers interrelated the tumor immune microenvironment (TIME) provides novel ideas for predicting the prognosis of gastric cancer (GC) and developing new treatment strategies. We analyzed the differential gene expression levels between the high and low StromalScore and ImmuneScore groups. Neutrophil elastase (ELANE) was evaluated as a potential biomarker by conducting intersection analysis of the protein-protein interaction network and univariate Cox regression analysis. The expression of ELANE was evaluated by immunohistochemistry. Its prognostic value was evaluated using Kaplan-Meier (K-M) survival curves and multivariate Cox regression analysis and its potential biological molecular mechanism was examined by gene set enrichment analysis (GSEA). We applied the CIBERSORT computing method to analyze the relationship between ELANE and tumor immune-infiltrating cells (TIICs). K-M survival curve showed that higher ELANE expression was closely related to shorter overall survival. The Cox regression analysis indicated that the high expression of ELANE was an independent prognostic risk factor in patients with GC. The GSEA revealed that genes in the ELANE high-expression group were involved in the signaling pathways regulating immune response; genes in the ELANE low-expression group were involved in the signaling pathways that regulate metabolism. ELANE might be participate in the change of TIME from immunodominant to metabolically dominant and its expression was closely related to tumor mutation burden and multiple TIICs. ELANE is a potential biomarker for predicting the GC patients' survival and prognosis. It influences the tumor immune cell infiltration in the TIME, and affects the TIME to maintain their immune status.
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Affiliation(s)
- Wangqiang Jia
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Qianwen Luo
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Jiang Wu
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Yuanchao Shi
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Quanlin Guan
- The First Clinical Medical College of Lanzhou University, Lanzhou, China.
- Department of Oncology Surgery, The First Hospital of Lanzhou University, No. 1, Donggang West Road, Lanzhou, 730000, Gansu Province, China.
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19
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Jiang Y, Zhou K, Sun Z, Wang H, Xie J, Zhang T, Sang S, Islam MT, Wang JY, Chen C, Yuan Q, Xi S, Li T, Xu Y, Xiong W, Wang W, Li G, Li R. Non-invasive tumor microenvironment evaluation and treatment response prediction in gastric cancer using deep learning radiomics. Cell Rep Med 2023; 4:101146. [PMID: 37557177 PMCID: PMC10439253 DOI: 10.1016/j.xcrm.2023.101146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 06/06/2023] [Accepted: 07/12/2023] [Indexed: 08/11/2023]
Abstract
The tumor microenvironment (TME) plays a critical role in disease progression and is a key determinant of therapeutic response in cancer patients. Here, we propose a noninvasive approach to predict the TME status from radiological images by combining radiomics and deep learning analyses. Using multi-institution cohorts of 2,686 patients with gastric cancer, we show that the radiological model accurately predicted the TME status and is an independent prognostic factor beyond clinicopathologic variables. The model further predicts the benefit from adjuvant chemotherapy for patients with localized disease. In patients treated with checkpoint blockade immunotherapy, the model predicts clinical response and further improves predictive accuracy when combined with existing biomarkers. Our approach enables noninvasive assessment of the TME, which opens the door for longitudinal monitoring and tracking response to cancer therapy. Given the routine use of radiologic imaging in oncology, our approach can be extended to many other solid tumor types.
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Affiliation(s)
- Yuming Jiang
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Kangneng Zhou
- School of Computer and Communication Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Zepang Sun
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hongyu Wang
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Jingjing Xie
- Graduate Group of Epidemiology, University of California Davis, Davis, CA, USA
| | - Taojun Zhang
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shengtian Sang
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Md Tauhidul Islam
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Jen-Yeu Wang
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Chuanli Chen
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qingyu Yuan
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Sujuan Xi
- The Reproductive Medical Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Tuanjie Li
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yikai Xu
- Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wenjun Xiong
- Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wei Wang
- Department of Gastric Surgery, and State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Guoxin Li
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Ruijiang Li
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
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Mo X, Yuan K, Hu D, Huang C, Luo J, Liu H, Li Y. Identification and validation of immune-related hub genes based on machine learning in prostate cancer and AOX1 is an oxidative stress-related biomarker. Front Oncol 2023; 13:1179212. [PMID: 37583929 PMCID: PMC10423936 DOI: 10.3389/fonc.2023.1179212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 07/12/2023] [Indexed: 08/17/2023] Open
Abstract
To investigate potential diagnostic and prognostic biomarkers associated with prostate cancer (PCa), we obtained gene expression data from six datasets in the Gene Expression Omnibus (GEO) database. The datasets included 127 PCa cases and 52 normal controls. We filtered for differentially expressed genes (DEGs) and identified candidate PCa biomarkers using a least absolute shrinkage and selector operation (LASSO) regression model and support vector machine recursive feature elimination (SVM-RFE) analyses. A difference analysis was conducted on these genes in the test group. The discriminating ability of the train group was determined using the area under the receiver operating characteristic curve (AUC) value, with hub genes defined as those having an AUC greater than 85%. The expression levels and diagnostic utility of the biomarkers in PCa were further confirmed in the GSE69223 and GSE71016 datasets. Finally, the invasion of cells per sample was assessed using the CIBERSORT algorithm and the ESTIMATE technique. The possible prostate cancer (PCa) diagnostic biomarkers AOX1, APOC1, ARMCX1, FLRT3, GSTM2, and HPN were identified and validated using the GSE69223 and GSE71016 datasets. Among these biomarkers, AOX1 was found to be associated with oxidative stress and could potentially serve as a prognostic biomarker. Experimental validations showed that AOX1 expression was low in PCa cell lines. Overexpression of AOX1 significantly reduced the proliferation and migration of PCa cells, suggesting that the anti-tumor effect of AOX1 may be attributed to its impact on oxidative stress. Our study employed a comprehensive approach to identify PCa biomarkers and investigate the role of cell infiltration in PCa.
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Affiliation(s)
- Xiaocong Mo
- Department of Oncology, the First Affiliated Hospital of Jinan University, Jinan University, Guangdong, Guangzhou, China
| | - Kaisheng Yuan
- Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Jinan University, Guangdong, Guangzhou, China
| | - Di Hu
- Department of Neurology and Stroke Centre, the First Affiliated Hospital of Jinan University, Jinan University, Guangdong, Guangzhou, China
| | - Cheng Huang
- Department of Neurology and Stroke Centre, the First Affiliated Hospital of Jinan University, Jinan University, Guangdong, Guangzhou, China
| | - Juyu Luo
- Department of Neurology and Stroke Centre, the First Affiliated Hospital of Jinan University, Jinan University, Guangdong, Guangzhou, China
| | - Hang Liu
- Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China
| | - Yin Li
- Department of Oncology, the First Affiliated Hospital of Jinan University, Jinan University, Guangdong, Guangzhou, China
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21
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Wang SY, Wang YX, Shen A, Jian R, An N, Yuan SQ. Construction and validation of a prognostic prediction model for gastric cancer using a series of genes related to lactate metabolism. Heliyon 2023; 9:e16157. [PMID: 37234661 PMCID: PMC10205640 DOI: 10.1016/j.heliyon.2023.e16157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Background Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. The commonly used tumor-node-metastasis (TNM) staging and some common biomarkers have a certain value in predicting the prognosis of GC patients, but they gradually fail to meet the clinical demands. Therefore, we aim to construct a prognostic prediction model for GC patients. Methods A total of 350 cases were included in the STAD (Stomach adenocarcinoma) entire cohort of TCGA (The Cancer Genome Atlas), including the STAD training cohort of TCGA (n = 176) and the STAD testing cohort of TCGA (n = 174). GSE15459 (n = 191), and GSE62254 (n = 300) were for external validation. Results Through differential expression analysis and univariate Cox regression analysis in the STAD training cohort of TCGA, we screened out five genes among 600 genes related to lactate metabolism for the construction of our prognostic prediction model. The internal and external validations showed the same result, that is, patients with higher risk score were associated with poor prognosis (all p < 0.05), and our model works well without regard of patients' age, gender, tumor grade, clinical stage or TNM stage, which supports the availability, validity and stability of our model. Gene function analysis, tumor-infiltrating immune cells analysis, tumor microenvironment analysis and clinical treatment exploration were performed to improve the practicability of the model, and hope to provide a new basis for more in-depth study of the molecular mechanism for GC and for clinicians to formulate more reasonable and individualized treatment plans. Conclusions We screened out and used five genes related to lactate metabolism to develop a prognostic prediction model for GC patients. The prediction performance of the model is confirmed by a series of bioinformatics and statistical analysis.
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Affiliation(s)
- Si-yu Wang
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Yu-xin Wang
- The First Hospital of Jilin University, Changchun, 130000, China
| | - Ao Shen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Rui Jian
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Nan An
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Shu-qiang Yuan
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
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22
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Li Z, Huang L, Li J, Yang W, Li W, Long Q, Dai X, Wang H, Du G. Immunological role and prognostic value of the SKA family in pan-cancer analysis. Front Immunol 2023; 14:1012999. [PMID: 37180139 PMCID: PMC10169755 DOI: 10.3389/fimmu.2023.1012999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 02/27/2023] [Indexed: 05/15/2023] Open
Abstract
Background The spindle and kinetochore associated (SKA) complex, which plays important roles in proper chromosome segregation during mitosis by maintaining the stabilization of kinetochore-spindle microtubule attachment during mitosis, has recently been reported to exert regulatory effects on the initiation and progression of various human cancer types. Nevertheless, the prognostic significance and immune infiltration of the SKA family across cancers have not been well elucidated. Methods Using data from three large public datasets, including The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases, a novel scoring system (termed the SKA score) was developed to quantify the SKA family level across cancers. We then evaluated the prognostic impact of the SKA score on survival and assessed the effect of the SKA score on immunotherapy at the pan-cancer level using multiomics bioinformatic analyses. The correlation of the SKA score and the tumor microenvironment (TME) was also explored in depth. Potential small molecular compounds and chemotherapeutic agents were assessed by CTRP and GDSC analyses. Immunohistochemistry was performed to verify the expression of the SKA family genes. Results Our results demonstrated a close correlation between the SKA score and tumor development and prognosis in multiple cancers. The SKA score was positively related to cell cycle pathways and DNA replication across cancers, such as E2F targets, the G2M checkpoint, MYC targets V1/V2, mitotic spindles and DNA repair. Additionally, the SKA score was negatively related to the infiltration of various immune cells with antitumor effects in the TME. In addition, the potential value of the SKA score was identified to predict immunotherapy response for melanoma and bladder cancer. We also demonstrated a correlation between SKA1/2/3 and the response to drug treatment across cancers and the promising potential of the SKA complex and its genes as therapeutic targets in cancer. Immunohistochemistry demonstrated that the expression differences of SKA1/2/3 were significant between the breast cancer group and the paracancerous group. Conclusion The SKA score plays a critical role in 33 cancer types and is highly related to tumor prognosis. Patients with elevated SKA scores have a clear immunosuppressive TME. The SKA score may serve as a predictor for patients receiving anti-PD-1/L1 therapy.
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Affiliation(s)
- Zhengtian Li
- Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lanying Huang
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jiachen Li
- Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Wenkang Yang
- Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Weichao Li
- Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Qiuzhong Long
- Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xinyu Dai
- Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hongtao Wang
- Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Gang Du
- Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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23
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Liu J, Zhong L, Deng D, Zhang Y, Yuan Q, Shang D. The combined signatures of the tumour microenvironment and nucleotide metabolism-related genes provide a prognostic and therapeutic biomarker for gastric cancer. Sci Rep 2023; 13:6622. [PMID: 37095256 PMCID: PMC10126105 DOI: 10.1038/s41598-023-33213-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 04/09/2023] [Indexed: 04/26/2023] Open
Abstract
The tumour microenvironment (TME) is vital to tumour development and influences the immunotherapy response. Abnormal nucleotide metabolism (NM) not only promotes tumour cell proliferation but also inhibits immune responses in the TME. Therefore, this study aimed to determine whether the combined signatures of NM and the TME could better predict the prognosis and treatment response in gastric cancer (GC). 97 NM-related genes and 22 TME cells were evaluated in TCGA-STAD samples, and predictive NM and TME characteristics were determined. Subsequent correlation analysis and single-cell data analysis illustrated a link between NM scores and TME cells. Thereafter, NM and TME characteristics were combined to construct an NM-TME classifier. Patients in the NMlow/TMEhigh group exhibited better clinical outcomes and treatment responses, which could be attributed to the differences in immune cell infiltration, immune checkpoint genes, tumour somatic mutations, immunophenoscore, immunotherapy response rate and proteomap. Additionally, the NMhigh/TMElow group benefited more from Imatinib, Midostaurin and Linsitinib, while patients in the NMlow/TMEhigh group benefited more from Paclitaxel, Methotrexate and Camptothecin. Finally, a highly reliable nomogram was developed. In conclusion, the NM-TME classifier demonstrated a pretreatment predictive value for prognosis and therapeutic responses, which may offer novel strategies for strategizing patients with optimal therapies.
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Affiliation(s)
- Jifeng Liu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Lei Zhong
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Dawei Deng
- Department of Hepato-Biliary-Pancreas, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yunshu Zhang
- Department of Traditional Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
| | - Qihang Yuan
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
| | - Dong Shang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
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Armakolas A, Kotsari M, Koskinas J. Liquid Biopsies, Novel Approaches and Future Directions. Cancers (Basel) 2023; 15:1579. [PMID: 36900369 PMCID: PMC10000663 DOI: 10.3390/cancers15051579] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 02/22/2023] [Accepted: 03/01/2023] [Indexed: 03/06/2023] Open
Abstract
Cancer is among the leading causes of death worldwide. Early diagnosis and prognosis are vital to improve patients' outcomes. The gold standard of tumor characterization leading to tumor diagnosis and prognosis is tissue biopsy. Amongst the constraints of tissue biopsy collection is the sampling frequency and the incomplete representation of the entire tumor bulk. Liquid biopsy approaches, including the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating miRNAs, and tumor-derived extracellular vesicles (EVs), as well as certain protein signatures that are released in the circulation from primary tumors and their metastatic sites, present a promising and more potent candidate for patient diagnosis and follow up monitoring. The minimally invasive nature of liquid biopsies, allowing frequent collection, can be used in the monitoring of therapy response in real time, allowing the development of novel approaches in the therapeutic management of cancer patients. In this review we will describe recent advances in the field of liquid biopsy markers focusing on their advantages and disadvantages.
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Affiliation(s)
- Athanasios Armakolas
- Physiology Laboratory, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
- B' Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - Maria Kotsari
- Physiology Laboratory, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - John Koskinas
- B' Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece
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Duan H, Chen B, Wang W, Luo H. Identification of GNG7 as a novel biomarker and potential therapeutic target for gastric cancer via bioinformatic analysis and in vitro experiments. Aging (Albany NY) 2023; 15:1445-1474. [PMID: 36863706 PMCID: PMC10042700 DOI: 10.18632/aging.204545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 02/16/2023] [Indexed: 03/04/2023]
Abstract
Gastric cancer (GC) is one of the most common malignancies with unfavorable prognoses. The present study aimed to identify novel biomarkers or potential therapeutic targets in GC via bioinformatic analysis and in vitro experiments. The Gene Expression Omnibus and The Cancer Genome Atlas databases were used to screen the differentially expressed genes (DEGs). After protein-protein interaction network construction, both module and prognostic analyses were performed to identify prognosis-related genes in GC. The expression patterns and functions of G protein γ subunit 7 (GNG7) in GC were then visualized in multiple databases and further verified using in vitro experiments. A total of 897 overlapping DEGs were detected and 20 hub genes were identified via systematic analysis. After accessing the prognostic value of the hub genes using the online server Kaplan-Meier plotter, a six-gene prognostic signature was identified, which was also significantly correlated with the process of immune infiltration in GC. The results of open-access database analyses suggested that GNG7 is downregulated in GC; this downregulation was associated with tumor progression. Furthermore, the functional enrichment analysis unveiled that the GNG7-coexpressed genes or gene sets were closely correlated with the proliferation and cell cycle processes of GC cells. Finally, in vitro experiments further confirmed that GNG7 overexpression inhibited GC cell proliferation, colony formation, and cell cycle progression and induced apoptosis. As a tumor suppressor gene, GNG7 suppressed the growth of GC cells via cell cycle blockade and apoptosis induction and thus may be used as a potential biomarker and therapeutic target for GC.
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Affiliation(s)
- Houyu Duan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China
| | - Biao Chen
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China
| | - Wei Wang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China
| | - Hesheng Luo
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China
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Zhu Y, Xiao H, Yu T, Cai D, Zhou Q, Zhou G, Wang L. An immune risk score predicts survival of patients with diffuse large B-cell lymphoma. Leuk Res 2023; 125:107008. [PMID: 36630885 DOI: 10.1016/j.leukres.2022.107008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/22/2022] [Accepted: 12/28/2022] [Indexed: 12/30/2022]
Abstract
PURPOSE Providing accurate prognostic models is necessary for diffuse large B-cell lymphoma, but there are still many uncertainties. So far, none of the models include immune cells. Therefore, an immune risk score was constructed to predict the survival of patients. METHODS CIBERSORTx was chosen to estimate the proportion of 22 human immune cell subsets from public datasets and generate an immune risk score to predict patients' survival in a training cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model. RESULTS The prognostic model had high predictive ability in the training and validation cohorts. Subjects in the training cohort with high scores had a worse prognosis compared with subjects with low scores. The same result was also found in the three validation cohorts. Multivariable analysis suggested that the immune risk score was an independent prognostic factor. The merged score, including the immune risk score and the international prognostic index (IPI) risk category, had better predictive accuracy. CONCLUSIONS Our immune risk score promises to be a complement to current prognostic models.
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Affiliation(s)
- Yu Zhu
- Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Han Xiao
- Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Tingyu Yu
- Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Duo Cai
- Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Qiao Zhou
- Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Guangyu Zhou
- Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Li Wang
- Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China..
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Wang Z, Huang Z, Cao X, Zhang F, Cai J, Tang P, Yang C, Li S, Yu D, Yan Y, Shen B. A prognostic model based on necroptosis-related genes for prognosis and therapy in bladder cancer. BMC Urol 2023; 23:10. [PMID: 36709279 PMCID: PMC9883845 DOI: 10.1186/s12894-023-01175-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 01/09/2023] [Indexed: 01/30/2023] Open
Abstract
Bladder cancer, one of the most prevalent malignant cancers, has high rate of recurrence and metastasis. Owing to genomic instability and high-level heterogeneity of bladder cancer, chemotherapy and immunotherapy drugs sensitivity and lack of prognostic markers, the prognosis of bladder cancer is unclear. Necroptosis is a programmed modality of necrotic cell death in a caspase-independent form. Despite the fact that necroptosis plays a critical role in tumor growth, cancer metastasis, and cancer patient prognosis, necroptosis-related gene sets have rarely been studied in bladder cancer. As a result, the development of new necroptosis-related prognostic indicators for bladder cancer patients is critical. Herein, we assessed the necroptosis landscape of bladder cancer patients from The Cancer Genome Atlas database and classified them into two unique necroptosis-related patterns, using the consensus clustering. Then, using five prognosis-related genes, we constructed a prognostic model (risk score), which contained 5 genes (ANXA1, DOK7, FKBP10, MAP1B and SPOCD1). And a nomogram model was also developed to offer the clinic with a more useful prognostic indicator. We found that risk score was significantly associated with clinicopathological characteristics, TIME, and tumor mutation burden in patients with bladder cancer. Moreover, risk score was a valid guide for immunotherapy, chemotherapy, and targeted drugs. In our study, DOK7 was chosen to further verify our prognosis model, and functional assays indicated that knockdown the expression of DOK7 could prompt bladder cancer proliferation and migration. Our work demonstrated the potential role of prognostic model based on necroptosis genes in the prognosis, immune landscape and response efficacy of immunotherapy of bladder cancer.
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Affiliation(s)
- Zeyi Wang
- grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080 China
| | - Zhengnan Huang
- grid.24516.340000000123704535Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065 China
| | - Xiangqian Cao
- grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080 China
| | - Fang Zhang
- grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080 China
| | - Jinming Cai
- grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080 China
| | - Pengfei Tang
- grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080 China
| | - Chenkai Yang
- grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080 China
| | - Shengzhou Li
- grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080 China
| | - Dong Yu
- grid.73113.370000 0004 0369 1660Department of Precision Medicine, Center of Translation Medicine, Naval Medical University, Shanghai, 200082 China
| | - Yilin Yan
- grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080 China
| | - Bing Shen
- grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080 China ,grid.412478.c0000 0004 1760 4628Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080 China
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Xie R, Liu L, Lu X, He C, Li G. Identification of the diagnostic genes and immune cell infiltration characteristics of gastric cancer using bioinformatics analysis and machine learning. Front Genet 2023; 13:1067524. [PMID: 36685898 PMCID: PMC9845288 DOI: 10.3389/fgene.2022.1067524] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 12/05/2022] [Indexed: 01/06/2023] Open
Abstract
Background: Finding reliable diagnostic markers for gastric cancer (GC) is important. This work uses machine learning (ML) to identify GC diagnostic genes and investigate their connection with immune cell infiltration. Methods: We downloaded eight GC-related datasets from GEO, TCGA, and GTEx. GSE13911, GSE15459, GSE19826, GSE54129, and GSE79973 were used as the training set, GSE66229 as the validation set A, and TCGA & GTEx as the validation set B. First, the training set screened differentially expressed genes (DEGs), and gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG), disease Ontology (DO), and gene set enrichment analysis (GSEA) analyses were performed. Then, the candidate diagnostic genes were screened by LASSO and SVM-RFE algorithms, and receiver operating characteristic (ROC) curves evaluated the diagnostic efficacy. Then, the infiltration characteristics of immune cells in GC samples were analyzed by CIBERSORT, and correlation analysis was performed. Finally, mutation and survival analyses were performed for diagnostic genes. Results: We found 207 up-regulated genes and 349 down-regulated genes among 556 DEGs. gene ontology analysis significantly enriched 413 functional annotations, including 310 biological processes, 23 cellular components, and 80 molecular functions. Six of these biological processes are closely related to immunity. KEGG analysis significantly enriched 11 signaling pathways. 244 diseases were closely related to Ontology analysis. Multiple entries of the gene set enrichment analysis analysis were closely related to immunity. Machine learning screened eight candidate diagnostic genes and further validated them to identify ABCA8, COL4A1, FAP, LY6E, MAMDC2, and TMEM100 as diagnostic genes. Six diagnostic genes were mutated to some extent in GC. ABCA8, COL4A1, LY6E, MAMDC2, TMEM100 had prognostic value. Conclusion: We screened six diagnostic genes for gastric cancer through bioinformatic analysis and machine learning, which are intimately related to immune cell infiltration and have a definite prognostic value.
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Affiliation(s)
- Rongjun Xie
- Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of General Surgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Longfei Liu
- Department of General Surgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Xianzhou Lu
- Department of General Surgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Chengjian He
- Department of Intensive Care Medicine, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Guoxin Li
- Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
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Tan M, Lin X, Chen H, Ye W, Yi J, Li C, Liu J, Su J. Sterol regulatory element binding transcription factor 1 promotes proliferation and migration in head and neck squamous cell carcinoma. PeerJ 2023; 11:e15203. [PMID: 37090107 PMCID: PMC10117388 DOI: 10.7717/peerj.15203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 03/17/2023] [Indexed: 04/25/2023] Open
Abstract
Background Sterol-regulatory element-binding protein 1 (SREBP1) is a transcription factor involved in lipid metabolism that is encoded by sterol regulatory element binding transcription factor 1(SREBF1). SREBP1 overexpression is associated with the progression of several human tumors; however, the role of SREBP1 in head and neck squamous cell carcinoma (HNSC) remains unclear. Methods SREBF1 expression in pan-cancer was analyzed using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data, and the association between SREBF1 expression and clinical characteristics of HNSC patients was examined using the UALCAN database. Enrichment analysis of SREBF1-related genes was performed using the Cluster Profiler R package. TCGA database was used to investigate the relationship between immune cell infiltration and SREBF1 expression. CCK-8, flow cytometry, and wound healing assays were performed to investigate the effect of SREBF1 knockdown on the proliferation and migration of HNSC cells. Results SREBF1 was significantly upregulated in several tumor tissues, including HNSC, and SREBF1 overexpression was positively correlated with sample type, cancer stage, tumor grade, and lymph node stage in HNSC patients. Gene enrichment analysis revealed that SREBF1 is associated with DNA replication and homologous recombination. SREBF1 upregulation was positively correlated with the infiltration of cytotoxic cells, B cells, T cells, T helper cells, and NK CD56 bright cells in HNSC. Knockdown of SREBF1 inhibited the proliferation and migration of HNSC cells (Hep2 and TU212) and induced apoptosis by downregulating the expression of steroidogenic acute regulatory protein-related lipid transfer 4 (STARD4). Conclusions SREBF1 may promote HNSC proliferation, migration and inhibit apoptosis by upregulating STARD4 and affecting the level of immune cell infiltration.
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Yuan C, Yuan J, Xiao H, Li H, Jiang Y, Zhai R, Zhai J, Xing H, Huang J. Genomic analysis of matrix metalloproteinases affecting the prognosis and immunogenic profile of gastric cancer. Front Genet 2023; 14:1128088. [PMID: 37144126 PMCID: PMC10151559 DOI: 10.3389/fgene.2023.1128088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 04/04/2023] [Indexed: 05/06/2023] Open
Abstract
This study systematically and comprehensively analyzed the characteristics of matrix metalloproteinases (MMPs) in gastric cancer (GC) and revealed the relationship between MMPs and prognoses, clinicopathological features, tumor microenvironment, gene mutations, and drug therapy response in patients with GC. Based on the mRNA expression profiles of 45 MMP-related genes in GC, we established a model that classified GC patients into three groups based on cluster analysis of the mRNA expression profiles. The 3 groups of GC patients showed significantly different prognoses as well as tumor microenvironmental characteristics. Next, we used Boruta's algorithm and PCA method to establish an MMP scoring system and found that lower MMP scores were associated with better prognoses, lower clinical stages, better immune cell infiltration, lower degrees of immune dysfunction and rejection, and more genetic mutations. Whereas a high MMP score was the opposite. These observations were further validated with data from other datasets, showing the robustness of our MMP scoring system. Overall, MMP could be involved in the tumor microenvironment (TME), clinical features, and prognosis of GC. An in-depth study of MMP patterns can better understand the indispensable role of MMP in the development of GC and reasonably assess the survival prognosis, clinicopathological features, and drug efficacy of different patients, thus providing clinicians with a broader vision of GC progression and treatment.
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Affiliation(s)
- Chaofeng Yuan
- Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jialin Yuan
- Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Huijie Xiao
- Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Haitao Li
- Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yang Jiang
- Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Rongnan Zhai
- Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jinjing Zhai
- Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Hua Xing
- Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
- *Correspondence: Hua Xing, ; Jiannan Huang,
| | - Jiannan Huang
- Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
- *Correspondence: Hua Xing, ; Jiannan Huang,
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Zhang Y, Li L, Chu F, Zhang L, Zhang L, Wu H, Li K. The tumor microenvironment in gastrointestinal adenocarcinomas revealed a prognostic and immunotherapeutic biomarker. Aging (Albany NY) 2022; 14:10171-10216. [PMID: 36585927 PMCID: PMC9831739 DOI: 10.18632/aging.204463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 12/22/2022] [Indexed: 12/31/2022]
Abstract
Accumulated evidence has elucidated that the tumor microenvironment (TME) is great of clinical significance in predicting survival outcomes and therapeutic efficacy. Nonetheless, few studies have investigated the prognostic and immunotherapeutic signature correlated with TME phenotypes in gastrointestinal adenocarcinomas (GIAC). Here, by estimating the TME pattern of immune infiltration and expression in over 1,000 GIAC patients, we revealed three TME subgroups and identified six key differential genes. To predict the TME phenotypes, TMEscore was established and validated to be an independent prognostic factor, where the high TMEscore was characterized by immune activation and response to immunotherapy and accompanied with favorable prognosis in GIAC. Furthermore, TMEscore was confirmed to predict prognosis and immunotherapeutic response in six datasets. In summary, depicting TME landscape of GIAC patients may be beneficial for interpreting survival and immunotherapeutic response, and provide new strategies for clinical treatment of GIAC.
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Affiliation(s)
- Yong Zhang
- Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China,Medical Key Laboratory for Diagnosis and Treatment of Colorectal Cancer in Henan Province, Zhengzhou 450007, China,Zhengzhou Key Laboratory for Diagnosis, Treatment and Research of Colorectal Cancer, Zhengzhou 450007, China,Branch Center of Advanced Medical Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
| | - Lu Li
- Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China,Medical Key Laboratory for Diagnosis and Treatment of Colorectal Cancer in Henan Province, Zhengzhou 450007, China,Zhengzhou Key Laboratory for Diagnosis, Treatment and Research of Colorectal Cancer, Zhengzhou 450007, China
| | - Feifei Chu
- Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China,Medical Key Laboratory for Diagnosis and Treatment of Colorectal Cancer in Henan Province, Zhengzhou 450007, China,Zhengzhou Key Laboratory for Diagnosis, Treatment and Research of Colorectal Cancer, Zhengzhou 450007, China
| | - Lei Zhang
- Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China,Medical Key Laboratory for Diagnosis and Treatment of Colorectal Cancer in Henan Province, Zhengzhou 450007, China,Zhengzhou Key Laboratory for Diagnosis, Treatment and Research of Colorectal Cancer, Zhengzhou 450007, China
| | - Li Zhang
- Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China,Medical Key Laboratory for Diagnosis and Treatment of Colorectal Cancer in Henan Province, Zhengzhou 450007, China,Zhengzhou Key Laboratory for Diagnosis, Treatment and Research of Colorectal Cancer, Zhengzhou 450007, China
| | - Huili Wu
- Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China,Medical Key Laboratory for Diagnosis and Treatment of Colorectal Cancer in Henan Province, Zhengzhou 450007, China,Zhengzhou Key Laboratory for Diagnosis, Treatment and Research of Colorectal Cancer, Zhengzhou 450007, China
| | - Kunkun Li
- Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China,Medical Key Laboratory for Diagnosis and Treatment of Colorectal Cancer in Henan Province, Zhengzhou 450007, China,Zhengzhou Key Laboratory for Diagnosis, Treatment and Research of Colorectal Cancer, Zhengzhou 450007, China
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Yuan B, Qin H, Zhang J, Zhang M, Yang Y, Teng X, Yu H, Huang W, Wang Y. m 6A regulators featured by tumor immune microenvironment landscapes and correlated with immunotherapy in non-small cell lung cancer (NSCLC). Front Oncol 2022; 12:1087753. [PMID: 36591468 PMCID: PMC9800857 DOI: 10.3389/fonc.2022.1087753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 11/30/2022] [Indexed: 12/23/2022] Open
Abstract
Introduction Recent research has confirmed the critical role that epigenetic factors play in regulating the immune response. Nonetheless, what role m6A methylation modification might play in the immune response of non-small cell lung cancer (NSCLC) remains vague. Methods Herein, the gene expression, copy number variations (CNVs), and somatic mutations of 31 m6A regulators in NSCLC and adjacent control samples from the GEO and TCGA databases were comprehensively explored. Using consensus clustering, m6A modification patterns were identified. Correlations between m6A modification patterns and immune cell infiltration traits in the tumor immune microenvironment (TME) were systematically analyzed. Differentially expressed genes were verified and screened by random forest and cox regression analysis by comparing different m6A modification patterns. Based on the retained gene panel, a risk model was built, and m6Ascore for each sample was calculated. The function of m6Ascore in NSCLC prognosis, tumor somatic mutations, and chemotherapy/immunotherapy response prediction were evaluated. Results Consensus clustering classified all NSCLC samples into two m6A clusters (m6A_clusterA and m6A_clusterB) according to the expression levels of 25 m6A regulator genes. Hierarchical clustering further divides the NSCLC samples into two m6A gene clusters: m6AgeneclusterA and m6AgeneclusterB. A panel of 83 genes was screened from the 194 differentially expressed genes between m6A gene clusters. Based on this, a risk score model was established. m6A modification clusters, m6A gene clusters, and m6Ascore calculated from the risk model were able to predict tumor stages, immune cell infiltration, clinical prognosis, and tumor somatic mutations. NSCLC patients with high m6Ascore have poor drug resistance to chemotherapy drugs (Cisplatin and Gemcitabine) and exhibit considerable therapeutic benefits and favorable clinical responses to anti-PD1 or anti-CTLA4 immunotherapy. Discussion In conclusion, methylation modification patterns mediated by the m6A regulators in individuals play a non-negligible role in prognosis prediction and immunotherapy response, which will facilitate personalized treatment and immunotherapeutic strategies for NSCLC patients in the future.
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Affiliation(s)
- Baowen Yuan
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hao Qin
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingyao Zhang
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Min Zhang
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yunkai Yang
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xu Teng
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Hefen Yu
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Wei Huang
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Yan Wang
- Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Pyroptosis and Its Role in Cervical Cancer. Cancers (Basel) 2022; 14:cancers14235764. [PMID: 36497244 PMCID: PMC9739612 DOI: 10.3390/cancers14235764] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/21/2022] [Accepted: 11/21/2022] [Indexed: 11/25/2022] Open
Abstract
Pyroptosis, an inflammatory programmed cell death, is characterized by the caspase-mediated pore formation of plasma membranes and the release of large quantities of inflammatory mediators. In recent years, the morphological characteristics, induction mechanism and action process of pyroptosis have been gradually unraveled. As a malignant tumor with high morbidity and mortality, cervical cancer is seriously harmful to women's health. It has been found that pyroptosis is closely related to the initiation and development of cervical cancer. In this review the mechanisms of pyroptosis and its role in the initiation, progression and treatment application of cervical cancer are summarized and discussed.
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Todosenko N, Yurova K, Khaziakhmatova O, Malashchenko V, Khlusov I, Litvinova L. Heparin and Heparin-Based Drug Delivery Systems: Pleiotropic Molecular Effects at Multiple Drug Resistance of Osteosarcoma and Immune Cells. Pharmaceutics 2022; 14:pharmaceutics14102181. [PMID: 36297616 PMCID: PMC9612132 DOI: 10.3390/pharmaceutics14102181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/29/2022] [Accepted: 10/10/2022] [Indexed: 11/23/2022] Open
Abstract
One of the main problems of modern health care is the growing number of oncological diseases both in the elderly and young population. Inadequately effective chemotherapy, which remains the main method of cancer control, is largely associated with the emergence of multidrug resistance in tumor cells. The search for new solutions to overcome the resistance of malignant cells to pharmacological agents is being actively pursued. Another serious problem is immunosuppression caused both by the tumor cells themselves and by antitumor drugs. Of great interest in this context is heparin, a biomolecule belonging to the class of glycosaminoglycans and possessing a broad spectrum of biological activity, including immunomodulatory and antitumor properties. In the context of the rapid development of the new field of “osteoimmunology,” which focuses on the collaboration of bone and immune cells, heparin and delivery systems based on it may be of intriguing importance for the oncotherapy of malignant bone tumors. Osteosarcoma is a rare but highly aggressive, chemoresistant malignant tumor that affects young adults and is characterized by constant recurrence and metastasis. This review describes the direct and immune-mediated regulatory effects of heparin and drug delivery systems based on it on the molecular mechanisms of (multiple) drug resistance in (onco) pathological conditions of bone tissue, especially osteosarcoma.
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Affiliation(s)
- Natalia Todosenko
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia
| | - Kristina Yurova
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia
| | - Olga Khaziakhmatova
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia
| | - Vladimir Malashchenko
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia
| | - Igor Khlusov
- Department of Morphology and General Pathology, Siberian State Medical University, 634050 Tomsk, Russia
| | - Larisa Litvinova
- Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia
- Correspondence:
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Xiang Z, Cha G, Wang Y, Gao J, Jia J. Characterizing the Crosstalk of NCAPG with Tumor Microenvironment and Tumor Stemness in Stomach Adenocarcinoma. Stem Cells Int 2022; 2022:1888358. [PMID: 36238529 PMCID: PMC9551677 DOI: 10.1155/2022/1888358] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 09/16/2022] [Indexed: 12/24/2022] Open
Abstract
Background Nonstructural maintenance of non-SMC condensin I complex subunit G (NCAPG) exerts critical effects on cancer progression. However, its biological roles in tumorigenesis and metastasis remain unclear. Thus, we aimed to assess the prognostic utility of NCAPG in stomach adenocarcinoma (STAD) and its potential as a tumor biomarker. Methods Pan-cancer expression profile dataset from public databases and corresponding clinical information were extracted. Single-sample gene set enrichment analysis (ssGSEA) was performed for the evaluation of immune correlations pan-cancer. Subsequently, we focused on STAD and evaluated the methylation profiles, copy number variants (CNVs), and single nucleotide variants (SNVs). Immune features were analyzed between high and low NCAPG expression groups. Differential analysis was performed between high and low expression groups to identify differentially expressed genes (DEGs). Prognostic DEGs were screened by univariate analysis, and an NCAPG-based risk model was constructed based on the prognostic DEGs and LASSO analysis. Results NCAPG expression in STAD was significantly and positively correlated with four immune checkpoints, namely, CTLA4, PDCD1, LAG3, and CD276, but was negatively correlated with the infiltration of most immune cells. High and low NCAPG expression groups had differential overall survival, tumor mutation burden, and differential enrichment of therapeutic-related pathways. An immune risk scoring model related to NCAPG expression and immune score was constructed which showed a favorable performance in predicting STAD prognosis as well as predicting the response to immunotherapy. In addition, we found a higher mRNA stemness index (mRNAsi) in the high-risk group and a positive correlation between NCAPG expression and mRNAsi. Conclusion NCAPG was suggested to be involved in the regulation of tumor microenvironment in STAD. High NCAPG expression was related to high tumor stemness and good prognosis. The immune risk model had a potential to predict STAD prognosis and help directing therapeutic treatment.
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Affiliation(s)
- Zheng Xiang
- Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China 233000
| | - Genlan Cha
- Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China 233000
| | - Yihao Wang
- Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China 233000
| | - Jikai Gao
- Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China 233000
| | - Jianguang Jia
- Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China 233000
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Zhang J, Cai X, Cui W, Wei Z. Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer. Genes (Basel) 2022; 13:genes13101786. [PMID: 36292671 PMCID: PMC9601900 DOI: 10.3390/genes13101786] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/25/2022] [Accepted: 09/29/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Gastric cancer remains the most prevalent and highly lethal disease worldwide. MAP4K4, a member of Ste20, plays an important role in various pathologies, including cancer. However, its role in gastric cancer is not yet fully elucidated. Therefore, this study aims to determine the tumor-promoting role of MAP4K4 in gastric cancer and whether it can be used as a new and reliable biomarker to predict the prognosis of gastric cancer. For this purpose, we divide the samples into high- and low-expression groups according to the expression level of MAP4K4. The association of MAP4K4 expression with prognosis is assessed using the Kaplan–Meier survival analysis. Furthermore, immune infiltration analysis using ESTIMATE is conducted to evaluate the tumor immune scores of the samples. Results: The findings reveal a significantly higher expression of MAP4K4 in tumor samples than in adjacent samples. The high-expression group was significantly enriched in tumor-related pathways, such as the PI3K-Akt signaling pathway. In addition, immune infiltration analysis revealed a positive correlation between immune scores and MAP4K4 expression. We also observed that miRNAs, such as miR-192-3p (R = −0.317, p-value 3.111 × 10−9), miR-33b-5p (R= −0.238, p-value 1.166 × 10−5), and miR-582-3p (R = −0.214, p-value 8.430 × 10−5), had potential negative regulatory effects on MAP4K4. Moreover, we identified several transcription factors, ubiquitinated proteins, and interacting proteins that might regulate MAP4K4. The relationship between MAP4K4 and DNA methylation was also identified. Finally, we verified the high expression of MAP4K4 and its effect on promoting cancer. Conclusion: MAP4K4 might be closely related to gastric cancer’s progression, invasion, and metastasis. Its high expression negatively impacts the prognosis of gastric cancer patients. This suggests MAP4K4 as an important prognostic factor for gastric cancer and could be regarded as a new potential prognostic detection and therapeutic target.
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Affiliation(s)
- Junping Zhang
- Cancer Research Institute, Henan Academy Institute of Chinese Medicine, Zhengzhou 450000, China
- School of Basic Medicine Sciences, Henan University of Chinese Medicine; Zhengzhou 450004, China
| | - Xiaoping Cai
- Cancer Research Institute, Henan Academy Institute of Chinese Medicine, Zhengzhou 450000, China
- School of Basic Medicine Sciences, Henan University of Chinese Medicine; Zhengzhou 450004, China
| | - Weifeng Cui
- Cancer Research Institute, Henan Academy Institute of Chinese Medicine, Zhengzhou 450000, China
- School of Basic Medicine Sciences, Henan University of Chinese Medicine; Zhengzhou 450004, China
| | - Zheng Wei
- Cancer Research Institute, Henan Academy Institute of Chinese Medicine, Zhengzhou 450000, China
- School of Basic Medicine Sciences, Henan University of Chinese Medicine; Zhengzhou 450004, China
- Correspondence:
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Zhao L, Luo H, Dong X, Zeng Z, Zhang J, Yi Y, Lin C. A novel necroptosis-related lncRNAs signature for survival prediction in clear cell renal cell carcinoma. Medicine (Baltimore) 2022; 101:e30621. [PMID: 36181033 PMCID: PMC9524942 DOI: 10.1097/md.0000000000030621] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common kind of kidney cancer with poor prognosis. Necroptosis is a newly observed type of programmed cell death in recent years. However, the effects of necroptosis-related lncRNAs (NRlncRNAs) on ccRCC have not been widely explored. The transcription profile and clinical information were obtained from The Cancer Genome Atlas. Necroptosis-related lncRNAs were identified by utilizing a co-expression network of necroptosis-related genes and lncRNAs. Univariate Cox regression, least absolute shrinkage, and selection operator regression and multivariate Cox regression were performed to screen out ideal prognostic necroptosis-related lncRNAss and develop a multi-lncRNA signature. Finally, 6 necroptosis-related lncRNA markers were established. Patients were separated into high- and low-risk groups based on the performance value of the median risk score. Kaplan-Meier analysis identified that high-risk patients had poorer prognosis than low-risk patients. Furthermore, the area under time-dependent receiver operating characteristic curve reached 0.743 at 1 year, 0.719 at 3 years, and 0.742 at 5 years, which indicating that they can be used to predict ccRCC prognosis. In addition, the proposed signature was related to immunocyte infiltration. A nomogram model was also established to provide a more beneficial prognostic indicator for the clinic. Altogether, in the present study, the 6-lncRNA prognostic risk signature are trustworthy and effective indicators for predicting the prognosis of ccRCC.
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Affiliation(s)
- Liwen Zhao
- Department of Urology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, China
| | - Huaijing Luo
- Department of Urology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, China
| | - Xingmo Dong
- Department of Urology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, China
| | - Zhihui Zeng
- Department of Urology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, China
| | - Jianlong Zhang
- Department of Urology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, China
| | - Yi Yi
- Department of Urology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, China
| | - Chaolu Lin
- Department of Urology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, China
- * Correspondence: Chaolu Lin, Department of Urology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, Fujian Province, China (e-mail: )
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Xin S, Mao J, Cui K, Li Q, Chen L, Li Q, Tu B, Liu X, Wang T, Wang S, Liu J, Song X, Song W. A cuproptosis-related lncRNA signature identified prognosis and tumour immune microenvironment in kidney renal clear cell carcinoma. Front Mol Biosci 2022; 9:974722. [PMID: 36188220 PMCID: PMC9515514 DOI: 10.3389/fmolb.2022.974722] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/31/2022] [Indexed: 11/13/2022] Open
Abstract
Kidney renal clear cell carcinoma (KIRC) is a heterogeneous malignant tumor with high incidence, metastasis, and mortality. The imbalance of copper homeostasis can produce cytotoxicity and cause cell damage. At the same time, copper can also induce tumor cell death and inhibit tumor transformation. The latest research found that this copper-induced cell death is different from the known cell death pathway, so it is defined as cuproptosis. We included 539 KIRC samples and 72 normal tissues from the Cancer Genome Atlas (TCGA) in our study. After identifying long non-coding RNAs (lncRNAs) significantly associated with cuproptosis, we clustered 526 KIRC samples based on the prognostic lncRNAs and obtained two different patterns (Cuproptosis.C1 and C2). C1 indicated an obviously worse prognostic outcome and possessed a higher immune score and immune cell infiltration level. Moreover, a prognosis signature (CRGscore) was constructed to effectively and accurately evaluate the overall survival (OS) of KIRC patients. There were significant differences in tumor immune microenvironment (TIME) and tumor mutation burden (TMB) between CRGscore-defined groups. CRGscore also has the potential to predict medicine efficacy.
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Affiliation(s)
- Sheng Xin
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Jiaquan Mao
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Kai Cui
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Qian Li
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Liang Chen
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Qinyu Li
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Bocheng Tu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Xiaming Liu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Tao Wang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Shaogang Wang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Jihong Liu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Xiaodong Song
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- *Correspondence: Xiaodong Song, ; Wen Song,
| | - Wen Song
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- *Correspondence: Xiaodong Song, ; Wen Song,
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Bir Yucel K, Karabork Kilic AC, Sutcuoglu O, Yazıcı O, Aydos U, Kilic K, Özdemir N. Effects of Sarcopenia, Myosteatosis, and the Prognostic Nutritional Index on Survival in Stage 2 and 3 Gastric Cancer Patients. Nutr Cancer 2022; 75:368-375. [PMID: 36093734 DOI: 10.1080/01635581.2022.2121845] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND We aimed to evaluate the relationship between sarcopenia, myosteatosis, and systemic inflammatory response biomarkers and their prognostic role in stage 2 and 3 gastric cancer patients. METHODS This study included 84 patients with stage 2 or 3 gastric cancer who underwent a gastrectomy. Computed tomography scans were used to determine the skeletal muscle index (SMI) at the third lumbar vertebra level for sarcopenia and myosteatosis. RESULTS Based on the Asian Working Group of Sarcopenia (AWGS2019) criteria, the sarcopenia incidence was 36.9% and that of myosteatosis 46.4%. Univariate analysis showed that sarcopenia (48 vs. 14 mo, p < 0.001), myosteatosis (45 vs. 16 mo, p = 0.016), a low prognostic nutritional index (60 vs. 15 mo, p = 0.003), stage 3 (104 vs. 21 mo, p = 0.013), and old age (45 vs. 16 mo, p = 0.015) were poor prognostic markers. Multivariate analysis revealed that sarcopenia (AWGS2019), age, and stage significantly affected overall survival (hazard ratio: 3.31, 95% CI: 1.85-5.1; 1.96, 95% CI: 1.06-6.63; 2.5, 95% CI: 1.2-5.1, respectively). CONCLUSION We showed that sarcopenia directly affects overall gastric cancer survival.
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Affiliation(s)
| | | | - Osman Sutcuoglu
- Department of Medical Oncology, Gazi University, Ankara, Turkey
| | - Ozan Yazıcı
- Department of Medical Oncology, Gazi University, Ankara, Turkey
| | - Uguray Aydos
- Department of Nuclear Medicine, Gazi University, Ankara, Turkey
| | - Koray Kilic
- Department of Radiology, Gazi University, Ankara, Turkey
| | - Nuriye Özdemir
- Department of Medical Oncology, Gazi University, Ankara, Turkey
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Song B, Tian L, Zhang F, Lin Z, Gong B, Liu T, Teng W. A novel signature to predict thyroid cancer prognosis and immune landscape using immune-related LncRNA pairs. BMC Med Genomics 2022; 15:183. [PMID: 35996170 PMCID: PMC9394074 DOI: 10.1186/s12920-022-01332-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 08/05/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Thyroid cancer (TC) is the most common endocrine malignancy worldwide. The incidence of TC is high and increasing worldwide due to continuous improvements in diagnostic technology. Therefore, identifying accurate prognostic predictions to stratify TC patients is important. METHODS Raw data were downloaded from the TCGA database, and pairwise comparisons were applied to identify differentially expressed immune-related lncRNA (DEirlncRNA) pairs. Then, we used univariate Cox regression analysis and a modified Lasso algorithm on these pairs to construct a risk assessment model for TC. We further used qRT‒PCR analysis to validate the expression levels of irlncRNAs in the model. Next, TC patients were assigned to high- and low-risk groups based on the optimal cutoff score of the model for the 1-year ROC curve. We evaluated the signature in terms of prognostic independence, predictive value, immune cell infiltration, immune status, ICI-related molecules, and small-molecule inhibitor efficacy. RESULTS We identified 14 DEirlncRNA pairs as the novel predictive signature. In addition, the qRT‒PCR results were consistent with the bioinformatics results obtained from the TCGA dataset. The high-risk group had a significantly poorer prognosis than the low-risk group. Cox regression analysis revealed that this immune-related signature could predict prognosis independently and reliably for TC. With the CIBERSORT algorithm, we found an association between the signature and immune cell infiltration. Additionally, immune status was significantly higher in low-risk groups. Several immune checkpoint inhibitor (ICI)-related molecules, such as PD-1 and PD-L1, showed a negative correlation with the high-risk group. We further discovered that our new signature was correlated with the clinical response to small-molecule inhibitors, such as sunitinib. CONCLUSIONS We have constructed a prognostic immune-related lncRNA signature that can predict TC patient survival without considering the technical bias of different platforms, and this signature also sheds light on TC's overall prognosis and novel clinical treatments, such as ICB therapy and small molecular inhibitors.
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Affiliation(s)
- Bo Song
- Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, People's Republic of China
| | - Lijun Tian
- Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, People's Republic of China
| | - Fan Zhang
- Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, People's Republic of China
| | - Zheyu Lin
- Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, People's Republic of China
| | - Boshen Gong
- Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, People's Republic of China
| | - Tingting Liu
- Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, People's Republic of China
| | - Weiping Teng
- Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, People's Republic of China.
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Li H, Xu B, Du J, Wu Y, Shao F, Gao Y, Zhang P, Zhou J, Tong X, Wang Y, Li Y. Autophagy-related prognostic signature characterizes tumor microenvironment and predicts response to ferroptosis in gastric cancer. Front Oncol 2022; 12:959337. [PMID: 36052243 PMCID: PMC9424910 DOI: 10.3389/fonc.2022.959337] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 07/20/2022] [Indexed: 12/26/2022] Open
Abstract
Background Gastric cancer (GC) is an important disease and the fifth most common malignancy worldwide. Autophagy is an important process for the turnover of intracellular substances. Autophagy-related genes (ARGs) are crucial in cancer. Accumulating evidence indicates the clinicopathological significance of the tumor microenvironment (TME) in predicting prognosis and treatment efficacy. Methods Clinical and gene expression data of GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. A total of 22 genes with differences in expression and prognosis were screened from 232 ARGs. Three autophagy patterns were identified using an unsupervised clustering algorithm and scored using principal component analysis to predict the value of autophagy in the prognosis of GC patients. Finally, the relationship between autophagy and ferroptosis was validated in gastric cancer cells. Results The expression of ARGs showed obvious heterogeneity in GC patients. Three autophagy patterns were identified and used to predict the overall survival of GC patients. These three patterns were well-matched with the immunophenotype. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses showed that the biological functions of the three autophagy patterns were different. A scoring system was then set up to quantify the autophagy model and further evaluate the response of the patients to the immunotherapy. Patients with high autophagy scores had a more severe tumor mutation burden and better prognosis. High autophagy scores were accompanied by high microsatellite instability. Patients with high autophagy scores had significantly higher PD-L1 expression and increased survival. The experimental results confirmed that the expression of ferroptosis genes was positively correlated with the expression of autophagy genes in different autophagy clusters, and inhibition of autophagy dramatically reversed the decrease in ferroptotic cell death and lipid accumulation. Conclusions Autophagy patterns are involved in TME diversity and complexity. Autophagy score can be used as an independent prognostic biomarker in GC patients and to predict the effect of immunotherapy and ferroptosis-based therapy. This might benefit individualized treatment for GC.
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Affiliation(s)
- Haoran Li
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Bing Xu
- Department of Clinical Laboratory, Hangzhou Women’s Hospital, Hangzhou, China
| | - Jing Du
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Yunyi Wu
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Fangchun Shao
- Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Yan Gao
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Ping Zhang
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Junyu Zhou
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Xiangmin Tong
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Ying Wang
- Department of Central Laboratory, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yanchun Li
- Department of Central Laboratory, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Ledenko M, Antwi SO, Arima S, Driscoll J, Furuse J, Klümpen HJ, Larsen FO, Lau DK, Maderer A, Markussen A, Moehler M, Nooijen LE, Shaib WL, Tebbutt NC, André T, Ueno M, Woodford R, Yoo C, Zalupski MM, Patel T. Sex-related disparities in outcomes of cholangiocarcinoma patients in treatment trials. Front Oncol 2022; 12:963753. [PMID: 36033540 PMCID: PMC9404243 DOI: 10.3389/fonc.2022.963753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/25/2022] [Indexed: 12/24/2022] Open
Affiliation(s)
- Matthew Ledenko
- Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, United States
| | - Samuel O. Antwi
- Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, United States
| | - Shiho Arima
- Department of Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Julia Driscoll
- Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, United States
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center (UMC), Amsterdam, Netherlands
| | - Finn Ole Larsen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
| | - David K. Lau
- Oncogenic Transcription Laboratory, Olivia Newton-John Cancer and Research Institute, Melbourne, VIC, Australia
- School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia
| | - Annett Maderer
- First Department of Medicine, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany
- Research Center for Immunotherapy (FZI), University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Alice Markussen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Markus Moehler
- First Department of Medicine, University Medical Center of the Johannes-Gutenberg University, Mainz, Germany
- Research Center for Immunotherapy (FZI), University Medical Center, Johannes Gutenberg-University, Mainz, Germany
| | - Lynn E. Nooijen
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
| | - Walid L. Shaib
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, United States
| | - Niall C. Tebbutt
- Department of Medical Oncology, Olivia Newton-John Cancer Centre at Austin Health, Heidelberg, VIC, Australia
| | - Thierry André
- Sorbonne University and Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Makoto Ueno
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Kanagawa, Japan
| | - Rachel Woodford
- National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC), Medical Foundation Building, University of Sydney, Camperdown, NSW, Australia
| | - Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Mark M. Zalupski
- Department of Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Tushar Patel
- Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, United States
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Jiang S, Ding X, Wu Q, Cheng T, Xu M, Huang J. Identifying immune cells-related phenotype to predict immunotherapy and clinical outcome in gastric cancer. Front Immunol 2022; 13:980986. [PMID: 36032097 PMCID: PMC9402937 DOI: 10.3389/fimmu.2022.980986] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/25/2022] [Indexed: 12/09/2022] Open
Abstract
Background The tumor microenvironment is mainly composed of tumor-infiltrating immune cells (TIICs), fibroblast, extracellular matrix, and secreted factors. TIICs are often associated with sensitivity to immunotherapy and the prognosis of multiple cancers, yet the predictive role of individual cells on tumor prognosis is limited. Methods Based on single-sample gene set enrichment analysis, we combined three Gene Expression Omnibus (GEO) cohorts to build a TIIC model for risk stratification and prognosis prediction. The performance of the TIIC model was validated using our clinical cohort and the TCGA cohort. To assess the predictive power of the TIIC model for immunotherapy, we plotted the receiver operating characteristic curve with the IMvigor210 and GSE135222 cohorts. Results Chemokines, tumor-infiltrating immune cells, and immunomodulators differed between the two TIIC groups. The TIIC model was vital for predicting the outcome of immunotherapy. In our clinical samples, we verified that the expression levels of PD-1 and PD-L1 were higher in the low TIIC score group than in the high TIIC score group, both in the tumor and stroma. Conclusions Collectively, the TIIC model could provide a novel idea for immune cell targeting strategies in gastric cancer and predict the survival outcome of patients.
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Affiliation(s)
- Sutian Jiang
- Department of Clinical Biobank & The Institute of Oncology, Affiliated Hospital of Nantong University, Nantong, China
- Department of Pathology, Lishui People’s Hospital, Lishui, China
| | - Xuzhong Ding
- Department of Clinical Biobank & The Institute of Oncology, Affiliated Hospital of Nantong University, Nantong, China
- Department of Gastrointestinal Surgery, Lishui People’s Hospital, Lishui, China
| | - Qianqian Wu
- Department of Clinical Biobank & The Institute of Oncology, Affiliated Hospital of Nantong University, Nantong, China
| | - Tong Cheng
- Department of Clinical Biobank & The Institute of Oncology, Affiliated Hospital of Nantong University, Nantong, China
| | - Manyu Xu
- Department of Clinical Biobank & The Institute of Oncology, Affiliated Hospital of Nantong University, Nantong, China
| | - Jianfei Huang
- Department of Clinical Biobank & The Institute of Oncology, Affiliated Hospital of Nantong University, Nantong, China
- *Correspondence: Jianfei Huang,
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Yu X, He S, Shen J, Huang Q, Yang P, Huang L, Pu D, Wang L, Li L, Liu J, Liu Z, Zhu L. Tumor vessel normalization and immunotherapy in gastric cancer. Ther Adv Med Oncol 2022; 14:17588359221110176. [PMID: 35872968 PMCID: PMC9297465 DOI: 10.1177/17588359221110176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 06/09/2022] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is a common malignant tumor, and patients with GC have a low survival rate due to limited effective treatment methods. Angiogenesis and immune evasion are two key processes in GC progression, and they act synergistically to promote tumor progression. Tumor vascular normalization has been shown to improve the efficacy of cancer immunotherapy, which in turn may be improved through enhanced immune stimulation. Therefore, it may be interesting to identify synergies between immunomodulatory agents and anti-angiogenic therapies in GC. This strategy aims to normalize the tumor microenvironment through the action of the anti-vascular endothelial growth factor while stimulating the immune response through immunotherapy and prolonging the survival of GC patients.
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Affiliation(s)
- Xianzhe Yu
- Department of Gastrointestinal Surgery, Chengdu Second People's Hospital, Chengdu, Sichuan, People's Republic of China
| | - Shan He
- Department of Gastrointestinal Surgery, Chengdu Second People's Hospital, Chengdu, Sichuan, People's Republic of China
| | - Jian Shen
- Department of Gastrointestinal Surgery, Chengdu Second People's Hospital, Chengdu, Sichuan, People's Republic of China
| | - Qiushi Huang
- Department of Gastrointestinal Surgery, Chengdu Second People's Hospital, Chengdu, Sichuan, People's Republic of China
| | - Peng Yang
- Department of Gastrointestinal Surgery, Chengdu Second People's Hospital, Chengdu, Sichuan, People's Republic of China
| | - Lin Huang
- West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Dan Pu
- West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Li Wang
- Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People's Republic of China
| | - Lu Li
- Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People's Republic of China
| | - Jinghua Liu
- Department of Hepatobiliary Surgery, Linyi People's Hospital, Linyi, Shandong 276000, People's Republic of China
| | - Zelong Liu
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Lingling Zhu
- Lung Cancer Center, West China Hospital of Sichuan University, No. 37, Guo Xue Xiang, Wuhou District, Chengdu, Sichuan 610041, People's Republic of China
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Xing J, Guo L, Jia Z, Li Y, Han Y. The Multi-Omics Landscape and Clinical Relevance of the Immunological Signature of Phagocytosis Regulators: Implications for Risk Classification and Frontline Therapies in Skin Cutaneous Melanoma. Cancers (Basel) 2022; 14:cancers14153582. [PMID: 35892841 PMCID: PMC9331497 DOI: 10.3390/cancers14153582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 07/09/2022] [Accepted: 07/20/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary In this study, we focused on exploring phagocytosis regulators’ expression and mutational characteristics in skin cutaneous melanoma samples and delineating two molecular subtypes based on expression characteristics. We determined the relationship between phagocytosis regulators and survival by survival analysis of molecular subtypes. We then constructed a survival model (PRRS) to further quantify the criteria. Moreover, we combined pathway analysis, immune infiltration analysis, and mutation analysis to deeply explore the effects of phagocytosis regulators on skin cutaneous melanoma samples. Abstract Tumor-associated macrophages (TAMs) have gained considerable attention as therapeutic targets. Monoclonal antibody treatments directed against tumor antigens contribute significantly to cancer cell clearance by activating macrophages to phagocytose tumor cells. Due to its complicated genetic and molecular pathways, skin cutaneous melanoma (SKCM) has not yet attained the expected clinical efficacy and prognosis when compared to other skin cancers. Therefore, we chose TAMs as an entrance point. This study aimed to thoroughly assess the dysregulation and regulatory role of phagocytosis regulators in SKCM, as well as to understand their regulatory patterns in SKCM. This study subtyped prognosis-related phagocytosis regulators to investigate prognostic differences between subtypes. Then, we screened prognostic factors and constructed phagocytosis-related scoring models for survival prediction using differentially expressed genes (DEGs) between subtypes. Additionally, we investigated alternative treatment options using chemotherapeutic drug response data and clinical cohort treatment data. We first characterized and generalized phagocytosis regulators in SKCM and extensively examined the tumor immune cell infiltration. We created two phagocytosis regulator-related system (PRRS) phenotypes and derived PRRS scores using a principal component analysis (PCA) technique. We discovered that subtypes with low PRRS scores had a poor prognosis and decreased immune checkpoint-associated gene expression levels. We observed significant therapeutic and clinical improvements in patients with higher PRRS scores. Our findings imply that the PRRS scoring system can be employed as an independent and robust prognostic biomarker, serving as a critical reference point for developing novel immunotherapeutic methods.
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Affiliation(s)
- Jiahua Xing
- The First Medical Center, Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China; (J.X.); (L.G.); (Y.L.)
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Lingli Guo
- The First Medical Center, Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China; (J.X.); (L.G.); (Y.L.)
| | - Ziqi Jia
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China;
| | - Yan Li
- The First Medical Center, Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China; (J.X.); (L.G.); (Y.L.)
| | - Yan Han
- The First Medical Center, Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China; (J.X.); (L.G.); (Y.L.)
- Correspondence:
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Zhang Y, Zou J, Chen R. An M0 macrophage-related prognostic model for hepatocellular carcinoma. BMC Cancer 2022; 22:791. [PMID: 35854246 PMCID: PMC9294844 DOI: 10.1186/s12885-022-09872-y] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 07/04/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The role of M0 macrophages and their related genes in the prognosis of hepatocellular carcinoma (HCC) remains poorly characterized. METHODS Multidimensional bioinformatic methods were used to construct a risk score model using M0 macrophage-related genes (M0RGs). RESULTS Infiltration of M0 macrophages was significantly higher in HCC tissues than in normal liver tissues (P = 2.299e-07). Further analysis revealed 35 M0RGs that were associated with HCC prognosis; two M0RGs (OLA1 and ATIC) were constructed and validated as a prognostic signature for overall survival of patients with HCC. Survival analysis revealed the positive relationship between the M0RG signature and unfavorable prognosis. Correlation analysis showed that this risk model had positive associations with clinicopathological characteristics, somatic gene mutations, immune cell infiltration, immune checkpoint inhibitor targets, and efficacy of common drugs. CONCLUSIONS The constructed M0RG-based risk model may be promising for the clinical prediction of prognoses and therapeutic responses in patients with HCC.
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Affiliation(s)
- Yiya Zhang
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.,Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.,Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Ju Zou
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.,Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Ruochan Chen
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. .,Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Zhao F, Dong Z, Li Y, Liu S, Guo P, Zhang D, Li S. Comprehensive Analysis of Molecular Clusters and Prognostic Signature Based on m7G-related LncRNAs in Esophageal Squamous Cell Carcinoma. Front Oncol 2022; 12:893186. [PMID: 35912250 PMCID: PMC9329704 DOI: 10.3389/fonc.2022.893186] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 06/24/2022] [Indexed: 01/19/2023] Open
Abstract
N7-Methylguanosine (m7G) and long non-coding RNAs (lncRNAs) have been widely reported to play an important role in cancer. However, there is little known about the relationship between m7G-related lncRNAs and esophageal squamous cell carcinoma (ESCC). In this study, we aimed to find new potential biomarkers and construct an m7G-related lncRNA prognostic signature for ESCC. Three molecular clusters were identified by consensus clustering of 963 m7G-related lncRNAs, of which cluster B is preferentially related to poorer prognosis, higher immune and stromal scores, higher mRNA levels of immune checkpoints, and higher immune infiltrate level. We constructed a robust and effective m7G-related lncRNA prognostic signature (m7G-LPS, including 7 m7G-related prognostic lncRNAs) and demonstrated its prognostic value and predictive ability in the GEO and TCGA cohorts. The risk score was able to serve as an independent risk factor for patients with ESCC and showed better prediction than the traditional clinical risk factors. The immune score, stromal score, the infiltration level of immune cells and expression of immune checkpoints were significantly higher in the high-risk subgroup compared to the low-risk subgroup. The establishment of nomogram further improved the performance of m7G-LPS and facilitated its clinical application. Finally, we used GTEx RNA-seq data and qRT-PCR experiments to verify the expression levels of 7 m7G-related lncRNAs. To a certain degree, m7G-lncRNAs can be used as prognostic markers and therapeutic targets for ESCC patients.
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Affiliation(s)
- Fangchao Zhao
- Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
- School of Clinical Medicine, Hebei Medical University, Shijiazhuang, China
| | - Zefang Dong
- Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
- School of Clinical Medicine, Hebei Medical University, Shijiazhuang, China
| | - Yishuai Li
- Department of Thoracic Surgery, Hebei Chest Hospital, Shijiazhuang, China
| | - Shiquan Liu
- Department of Thoracic Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Pengfei Guo
- Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
- School of Clinical Medicine, Hebei Medical University, Shijiazhuang, China
| | - Dengfeng Zhang
- Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
- School of Clinical Medicine, Hebei Medical University, Shijiazhuang, China
| | - Shujun Li
- Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
- *Correspondence: Shujun Li, , orcid.org/0000-0001-5959-3160
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Zhou L, Fang H, Guo F, Yin M, Long H, Weng G. Computational construction of TME-related lncRNAs signature for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma. J Clin Lab Anal 2022; 36:e24582. [PMID: 35808868 PMCID: PMC9396193 DOI: 10.1002/jcla.24582] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/20/2022] [Accepted: 06/21/2022] [Indexed: 12/19/2022] Open
Abstract
Background The tumor microenvironment (TME) is closely related to clear cell renal cell carcinoma (ccRCC) prognosis, and immunotherapy response. In current study, comprehensive bio‐informative analysis was adopted to construct a TME‐related lncRNA signature for immune checkpoint inhibitors (ICIs) and targeted drug responses in ccRCC patients. Methods The TME mRNAs were screened following the immune and stromal scores with the data from GSE15641, GSE29609, GSE36895, GSE46699, GSE53757, and The Cancer Genome Atlas (TCGA)‐kidney renal clear cell carcinoma (KIRC). And the TME‐related lncRNAs were recognized using correlation analysis. The TME‐related lncRNAs prognostic model was constructed using the training dataset. Kaplan–Meier analysis, principal‐component analysis, and time‐dependent receiver operating characteristic were used to evaluate the risk model. The immune cell infiltration in TME was evaluated using the single‐sample gene set enrichment analysis (ssGSEA), ESTIMATE, and microenvironment cell populations counter algorithm. The immunophenoscore (IPS) was used to assess the response to immunotherapy with the constructed model. Results In the current study, 364 TME‐related lncRNAs were selected based on the integrated bioinformatical analysis. Six TME‐related lncRNAs (LINC00460, LINC01094, AC008870.2, AC068792.1, and AC007637.1) were identified as the prognostic signature in the training dataset and subsequently verified in the testing and entire datasets. Patients in the high‐risk group exhibited poor overall survival and disease‐free survival than those in the low‐risk group. The 1‐, 3‐, and 5‐year areas under the curves of the prognostic signature in the entire dataset were 0.704, 0.683, and 0.750, respectively. The risk score independently predicted ccRCC survival based on univariate and multivariate Cox regression. GSEA analysis suggested that the high‐risk group was concentrated on immune‐related pathways. The high‐risk group were characterized by high immune cell infiltration, high TMB and somatic mutation counters, high IPS‐PD‐1 + CTLA4 scores, and immune checkpoints expression upregulation, reflecting the higher ICIs response. The half inhibitory concentrations of sunitinib, temsirolimus, and rapamycin were low in the high‐risk group. Conclusion The TME‐related lncRNAs signature constructed could reliably predict the prognosis and immunotherapy response and targeted ccRCC patients' therapy.
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Affiliation(s)
- Libin Zhou
- Department of Urology, The affiliated Lihuili Hospital, Ningbo University, Ningbo, China.,Department of Urology, Ningbo Medical Centre Lihuili Hospital, Ningbo, China
| | - Hualong Fang
- The First Affiliated Hospital of Nanchang, Nanchang, China
| | - Fei Guo
- Ningbo Medical Centre Lihuili Hospital/Ningbo Institute for Medicine & Biomedical Engineering Combined Innovation, Ningbo, China
| | - Min Yin
- Department of Urology, Ningbo Medical Centre Lihuili Hospital, Ningbo, China
| | - Huimin Long
- Department of Urology, Ningbo Medical Centre Lihuili Hospital, Ningbo, China
| | - Guobin Weng
- Department of Urology, The affiliated Yinzhou No 2 Hospital, Ningbo University, Ningbo, China.,Department of Urology, Ningbo Yinzhou No.2 Hospital, Ningbo, China
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The Potential Diagnostic Value of Immune-Related Genes in Interstitial Fibrosis and Tubular Atrophy after Kidney Transplantation. J Immunol Res 2022; 2022:7212852. [PMID: 35755170 PMCID: PMC9232312 DOI: 10.1155/2022/7212852] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/29/2022] [Accepted: 05/11/2022] [Indexed: 12/02/2022] Open
Abstract
Background Inflammation within areas of interstitial fibrosis and tubular atrophy (IF/TA) is associated with kidney allograft failure. The aim of this study was to reveal new diagnostic markers of IF/TA based on bioinformatics analysis. Methods Raw data of IF/TA samples after kidney transplantation and control samples after kidney transplantation were extracted from the Gene Expression Omnibus (GEO) database (GSE76882 and GSE120495 datasets), and genes that were differentially expressed between the two groups (DEGs) were screened. Gene Set Enrichment Analysis (GSEA), ESTIMATE and single sample GSEA (ssGSEA), least absolute shrinkage and selection operator (LASSO) regression analysis, and competing endogenous RNA (ceRNA) network were used to analyze the data. Results The results of GSEA revealed that multiple immune-related pathways were enriched in the IF/TA group, and subsequent immune landscape analysis also showed that the IF/TA group had higher immune and stromal scores and up to 15 types of immune cells occupied them, such as B cells, cytotoxic cells, and T cells. LASSO regression analysis selected 6 (including ANGPTL3, APOH, LTF, FCGR2B, HLA-DQA2, and EGF) out of 14 DE-IRGs as diagnostic genes to construct a diagnostic model. Then, receiver operating characteristic (ROC) curve analysis showed the powerful diagnostic value of the model, and the area under the curve (AUC) of a single diagnostic gene was greater than 0.75. The results of ingenuity pathway analysis (IPA) also indicated that DEGs were involved in the immune system and kidney disease-related pathways. Finally, we found multiple miRNAs that could regulate diagnostic genes from the ceRNA network. Conclusion This study identified 6 IF/TA-related genes, which might be used as a new diagnosis model in the clinical practice.
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Yuan Y, Yang B, Qi Z, Han Z, Cai J, Song J. KDELR1 Is an Independent Prognostic Predictor and Correlates With Immunity in Glioma. Front Oncol 2022; 12:783721. [PMID: 35814367 PMCID: PMC9263977 DOI: 10.3389/fonc.2022.783721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 05/23/2022] [Indexed: 11/20/2022] Open
Abstract
Background Gliomas are the most malignant central nervous system tumors. With the development of sequencing technology, more potential biomarkers related to the treatment, prognosis, and molecular classification of glioma have been identified. Here, we intend to investigate the potential biological function and clinical value of a new biomarker in glioma. Methods KDELR1 expression data and the corresponding clinical information were downloaded from public databases and then preprocessed using R language. Correlation, Kaplan–Meier survival, and Cox regression analyses were performed to explore the clinical significance of KDELR1 in glioma patients. Furthermore, the immune infiltration and microenvironment parameters were evaluated via TIMER and CIBERSORT. Immunohistochemistry was conducted to confirm the KDELR1 expression and its correlation with immunity infiltration and prognosis. Results KDELR1 was upregulated in glioma samples compared with normal brain tissues, and its expression was significantly correlated with age, the World Health Organization (WHO) grade, recurrence, necrosis, microvascular proliferation, molecular classification, isocitrate dehydrogenase (IDH) mutation, and 1p/19q codeletion status. In addition, survival analysis showed that glioma patients with KDELR1 overexpression had shorter overall survival (OS) and disease-free survival times, and Cox regression analysis revealed that KDELR1 acted as an independent prognostic factor of OS in glioma patients. Gene set enrichment analysis indicated a significant enrichment of metabolism-associated pathways. KDELR1 expression was positively associated with immune infiltration (including infiltration by CD8+ T cells, CD4+ T cells, macrophages, and so on) and microenvironment parameters (including stromal, immune, and ESTIMATE scores) in gliomas. The expression of KDELR1 and its correlation with the tumor grade and prognosis were confirmed by immunohistochemistry in clinical samples (n = 119, P < 0.05). Conclusions Taken together, these findings suggest that KDELR1 is correlated with the tumor grade, molecular classifications, and immune infiltration; highlighting that KDELR1 is a novel and promising biomarker for molecular classification, treatment, and prognostic assessment may further indicate the treating effect of immune therapy.
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Affiliation(s)
- Yifan Yuan
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, China
| | - Biao Yang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, China
| | - Zengxin Qi
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, China
| | - Zhenyuan Han
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
| | - Jiajun Cai
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, China
- *Correspondence: Jianping Song, ; Jiajun Cai,
| | - Jianping Song
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, China
- Neurosurgical Institute of Fudan University, Shanghai, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- *Correspondence: Jianping Song, ; Jiajun Cai,
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