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Wang XL, Zhang L, Shang Q. Circular RNA hsa_circRNA_101996 modulates gastric cancer cell proliferation and apoptosis through the miR-577/HMGN5 axis. World J Gastrointest Oncol 2025; 17:105933. [DOI: 10.4251/wjgo.v17.i5.105933] [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: 02/10/2025] [Revised: 03/19/2025] [Accepted: 03/20/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) are critical regulators in tumorigenesis, functioning as microRNA sponges or protein decoys. Although numerous circRNAs have been implicated in gastric cancer progression, the role of hsa_circRNA_101996 remains unclear. This study hypothesizes that hsa_circRNA_101996 promotes gastric cancer cell proliferation and apoptosis via the microRNA-577 (miR-577)/high mobility group nucleosome binding domain 5 (HMGN5) axis.
AIM To investigate the role of hsa_circRNA_101996 in gastric cancer proliferation and apoptosis through the miR-577/HMGN5 axis.
METHODS Forty-one paired gastric cancer tissues and adjacent non-cancerous tissues were analyzed. Differential circRNA expression was identified using GSE83521 and GSE89143 datasets. miR-577 and HMGN5 were predicted via CircInteractome and TargetScan. Functional experiments (MTT, colony formation, Western blot) and dual-luciferase reporter assays were performed in gastric cancer cell lines (OCUM-1, HSC-39). In vivo tumorigenesis was validated in nude mice. Statistical analysis included Student’s t-test and one-way ANOVA (P < 0.05).
RESULTS Hsa_circRNA_101996 was significantly upregulated in gastric cancer tissues and cell lines compared to adjacent non-cancerous tissues (P < 0.05). Dual-luciferase reporter assays validated the interactions among hsa_circRNA_101996, miR-577, and HMGN5. In vitro, gastric cancer cells overexpressing hsa_circRNA_101996 showed significantly increased proliferation and decreased apoptosis compared to controls (P < 0.05). Cells transfected with miR-577 mimics exhibited reduced proliferation and increased apoptosis (P < 0.05). Co-transfection with hsa_circRNA_101996 or HMGN5 reversed the effects of miR-577 mimics. In vivo, hsa_circRNA_101996-overexpressing tumors showed increased volume and HMGN5 expression (P < 0.05).
CONCLUSION Hsa_circRNA_101996 promotes gastric cancer progression by sponging miR-577 to upregulate HMGN5, suggesting a novel therapeutic target for gastric cancer.
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Affiliation(s)
- Xiao-Lei Wang
- Department of General Surgery, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China
| | - Lin Zhang
- Department of Oncology, The First People's Hospital of Changshu, Suzhou 215501, Jiangsu Province, China
| | - Qing Shang
- Department of General Surgery, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China
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Zhang R, Nie Y, Chen X, Jiang T, Wang J, Peng Y, Zhou G, Li Y, Zhao L, Chen B, Ni Y, Cheng Y, Xu Y, Zhu Z, Gao X, Wu Z, Li T, Zhao J, Liu C, Zhao G, Chen J, Zhao J, Ji G, Han X, He J, Li Y. A multicenter prospective clinical trial reveals cell-free DNA methylation markers for early esophageal cancer. J Clin Invest 2025; 135:e186816. [PMID: 39998886 PMCID: PMC11996849 DOI: 10.1172/jci186816] [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: 09/18/2024] [Accepted: 02/19/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUNDCurrent methods for detecting esophageal cancer (EC) are generally invasive or exhibit limited sensitivity and specificity, especially for the identification of early-stage tumors.METHODSWe identified potential methylated DNA markers (MDMs) from multiple genomic regions in a discovery cohort, and a diagnostic model was developed and verified in a model-verification cohort of 297 participants. The accuracy of the MDM panel was validated in a multicenter, prospective cohort (n = 1,429). The clinical performance of identified MDMs were compared with current tumor-associated protein markers.RESULTSFrom 31 significant differentially methylated EC-associated regions identified in the marker discovery, we trained and validated a 3-MDM diagnostic model that could discriminate among patients with EC and volunteers without EC in a multicenter clinical prospective cohort with a sensitivity of 85.5% and a specificity of 95.3%. This panel showed higher sensitivity in diagnosing early-stage tumors, with sensitivities of 56% for stage 0 and 77% for stage I, compared with the performance of current biochemical markers. In population with high risk for EC, the sensitivity and specificity were 85.68% and 93.61%, respectively.CONCLUSIONThe assessment of tumor-associated methylation status in blood samples can facilitate noninvasive and reliable diagnosis of early-stage EC, which warrants further development to expand screening and reduce mortality rates.TRIAL REGISTRATIONChiCTR2400083525.FUNDINGScience and technology funds of Beijing Municipal Science & Technology Commission, Administrative Commission of Zhongguancun Science Park. Project number: Z201100005420007.
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Affiliation(s)
- Ruixiang Zhang
- 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
| | - Yongzhan Nie
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Xiaobing Chen
- Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Tao Jiang
- Department of Thoracic Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi’an, Shaanxi, China
| | - Jinhai Wang
- Department of Gastroenterology, Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yuhui Peng
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Guangpeng Zhou
- BioChain (Beijing) Science & Technology Inc., Beijing, China
| | - Yong Li
- 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
| | - Lina Zhao
- Department of Radiation Oncology and
| | - Beibei Chen
- Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Yunfeng Ni
- Department of Thoracic Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi’an, Shaanxi, China
| | - Yan Cheng
- Department of Gastroenterology, Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yiwei Xu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Zhenyu Zhu
- BioChain (Beijing) Science & Technology Inc., Beijing, China
| | - Xianchun Gao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Zhen Wu
- BioChain (Beijing) Science & Technology Inc., Beijing, China
| | - Tianbao Li
- BioChain (Beijing) Science & Technology Inc., Beijing, China
| | - Jie Zhao
- BioChain (Beijing) Science & Technology Inc., Beijing, China
| | - Cantong Liu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Gang Zhao
- Department of Gastroenterology, Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Jiakuan Chen
- Department of Thoracic Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi’an, Shaanxi, China
| | - Jing Zhao
- Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Gang Ji
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Xiaoliang Han
- BioChain (Beijing) Science & Technology Inc., Beijing, China
| | - Jie He
- 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
| | - Yin Li
- 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
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Lu Q, Li L, Liang W, Xu G, Zhu J, Ma X, Tian W, Gao L, Tian M, Chen Z, Zang H. Rapid screening of esophageal squamous cell carcinoma by near-infrared spectroscopy combined with aquaphotomics. Talanta 2025; 285:127399. [PMID: 39708567 DOI: 10.1016/j.talanta.2024.127399] [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: 08/12/2024] [Revised: 12/13/2024] [Accepted: 12/14/2024] [Indexed: 12/23/2024]
Abstract
Esophageal cancer (EC), the fifth most common cause of cancer-related mortality in China, poses a significant threat to public health. Among the pathological types, esophageal squamous cell carcinoma (ESCC) is predominant, comprising approximately 90 % of cases. Screening is crucial for early detection, diagnosis and treatment, thereby reducing ESCC mortality. This study aimed to develop a rapid, accurate, and cost-effective method based on near-infrared (NIR) spectroscopy combined with aquaphotomics for ESCC screening. NIR spectra were obtained from plasma samples of both healthy controls and ESCC patients. Subsequently, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify the water matrix coordinates (WAMACS), thereby delineating the water absorption spectrum pattern (WASP) and constructing an aquagram. The results showed that the PLS-DA screening test model demonstrated high accuracy and precision rates of 95.12 % and 97.10 %, respectively, along with sensitivity and specificity rates of 97.10 % and 84.62 %. The area under the curve (AUC) achieved 0.9064. Aquaphotomic analysis revealed that the WASP of the healthy group predominantly exhibited strong absorption in regions indicative of strong hydrogen bonds (1460 nm, 1480 nm, 1494 nm), while the WASP of the ESCC group showed strong absorption in regions associated with strong hydrogen bonds, weak hydrogen bonds and free water, especially the regions of weak hydrogen bonds (1434 nm) and free water (1390 nm) were significantly different from those of the healthy group. The findings indicated that the rapid screening model for ESCC, integrating NIR spectroscopy with aquaphotomics, is both effective and feasible, with the WASP presenting as a potentially valuable biomarker for ESCC screening.
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Affiliation(s)
- Qingqing Lu
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Lian Li
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Shandong Engineering Research Center for Transdermal Drug Delivery Systems, Jinan, Shandong, 250000, China
| | - Wenyan Liang
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Guoning Xu
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Jing Zhu
- Department of Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China
| | - Xiaobo Ma
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Weilu Tian
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - Lele Gao
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Mengyin Tian
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Zhongjian Chen
- Experimental Research Center, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China.
| | - Hengchang Zang
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Shandong Engineering Research Center for Transdermal Drug Delivery Systems, Jinan, Shandong, 250000, China; National Glycoengineering Research Center, Shandong University, Jinan, Shandong, 250012, China.
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Saegusa Y, Imaoka Y, Ohira M, Kobayashi T, Honmyo N, Hamaoka M, Onoe T, Takei D, Oishi K, Abe T, Nakayama T, Akabane M, Sasaki K, Ohdan H. Cluster analysis of hepatocellular carcinoma prognosis using preoperative alpha-fetoprotein and des-gamma-carboxy prothrombin levels: a multi-institutional study. J Gastrointest Surg 2025; 29:101980. [PMID: 39884550 DOI: 10.1016/j.gassur.2025.101980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 01/23/2025] [Accepted: 01/25/2025] [Indexed: 02/01/2025]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) remains the leading cause of cancer-related mortality worldwide and is characterized by high recurrence rates after curative resection. The tumor markers des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are crucial for HCC diagnosis and prognosis. However, their roles in the modern era of HCC epidemiology require reevaluation. METHODS This multi-institutional retrospective study analyzed 1515 patients who underwent hepatectomy for primary HCC. Patients were classified into 4 clusters using k-means analysis based on preoperative DCP and AFP levels. Clinicopathologic characteristics, overall survival (OS), and recurrence rate (RR) were evaluated using Cox proportional hazards models and area under the receiver operating characteristic curve (AUROC) comparisons. RESULTS Cluster 3 (concurrent elevations of DCP and AFP) had the poorest 5-year OS (52.8%) and the highest RR (79.3%), whereas cluster 4 (low levels of both markers) had the most favorable outcomes, with a 5-year OS rate of 71.5% and an RR of 55.7%. Cluster 1 (elevated DCP alone) was associated with larger tumors (median of 45 mm) and more frequent vascular invasion (43%) than cluster 2 (elevated AFP alone, median tumor size of 24 mm, and vascular invasion of 36%). DCP was a stronger predictor of 5-year OS in patients with preserved liver function (AUROC, 0.63), whereas AFP was more effective in stratifying RR in patients with impaired liver function (AUROC, 0.57). Non-B, non-C hepatitis (NBNC)-related HCC exhibited a distinct biomarker profile, with an elevated DCP level correlating with a higher 5-year RR (67%) than other etiologies. CONCLUSION Our study introduces tumor marker clustering as a novel analytical approach, providing a nuanced understanding of AFP and DCP's combined utility in predicting prognosis and recurrence. Our findings highlight the independent and complementary roles of these biomarkers, particularly in NBNC-related HCC and in cases with impaired liver function. AFP and DCP remain crucial tools for recurrence risk assessment, guiding personalized management strategies, such as surveillance, neoadjuvant therapies, and tailored postoperative interventions.
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Affiliation(s)
- Yoshitaka Saegusa
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuki Imaoka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Division of Abdominal Transplant, Stanford University, Stanford, CA, United States
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naruhiko Honmyo
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Michinori Hamaoka
- Department of Gastroenterological, Breast and Transplant Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Takashi Onoe
- Department of Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure City, Japan
| | - Daisuke Takei
- Department of Surgery, Onomichi General Hospital, Onomichi City, Japan
| | - Koichi Oishi
- Department of Surgery, Chugoku Rosai Hospital, Kure City, Japan
| | - Tomoyuki Abe
- Department of Surgery, National Hospital Organization, Higashihiroshima Medical Center, Higashihiroshima, Japan
| | - Toshihiro Nakayama
- Division of Abdominal Transplant, Stanford University, Stanford, CA, United States
| | - Miho Akabane
- Division of Abdominal Transplant, Stanford University, Stanford, CA, United States
| | - Kazunari Sasaki
- Division of Abdominal Transplant, Stanford University, Stanford, CA, United States
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Yan H, Lin Z, Zhang J, Zhu P, Chen Y, Liao J. Unveiling the key roles in esophageal cancer drug resistance from a genetic perspective: the interplay between cytokines and immune cell phenotypes. Discov Oncol 2025; 16:443. [PMID: 40169455 PMCID: PMC11961861 DOI: 10.1007/s12672-025-02074-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 03/05/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND Esophageal cancer (EC) is a common malignant tumor, often diagnosed in its late stages due to the subtlety of early symptoms. Traditional chemotherapy inflicts significant harm on the organism; however, the emergence of targeted and immune therapies has conferred considerable survival advantages for patients with EC. However, the prolonged exposure of immune cells to the tumor microenvironment (TME) results in functional deterioration, thereby causing drug resistance and notably diminishing the therapeutic outcomes. Therefore, it is necessary to gain an in-depth understanding of the immune microenvironment of EC to find ways to overcome the development of resistance. OBJECTIVE This study aimed to explore the causal relationships between cytokines, immune cell phenotypes, and the development of EC, with particular emphasis on their role in tumor progression and drug resistance. Using Mendelian randomization, we sought to identify key immune-related factors implicated in EC pathogenesis and evaluate their potential as therapeutic targets for overcoming resistance to treatment. RESULTS Through univariable MR, we found that two cytokines and twenty-two immune cell phenotypes are significantly associated with the incidence of EC. Further bidirectional MR analysis indicated interactions between two cytokines and five immune cells. Lastly, two-step MR analysis showed that there are mediating pathways in both directions between cytokines and immune cell phenotypes. CONCLUSION This research deepens the understanding of the mechanisms underlying the interactions between key cytokines and immune cells associated with the onset of EC. The research provides new insights into the issue of drug resistance within the esophageal cancer TME and offers novel perspectives for the development of targeted and immune-based therapies for EC.
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Affiliation(s)
- Huishen Yan
- Department of Medical Science, Yangzhou Polytechnic College, Yangzhou, 225009, China
| | - Zhiwu Lin
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Jieying Zhang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Peiquan Zhu
- Department of Thoracic Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Yuquan Chen
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing & Health Sciences, Monash University, Level 1, 553 St Kilda Road, Melbourne, VIC, 3004, Australia.
| | - Jingyuan Liao
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Street Taiping No.25, Region Jiangyang, Luzhou, 646099, Sichuan Province, China.
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Huang XY, Chen SX, Wang ZY, Lu YS, Liu CT, Chen SZ. PIWI-interacting RNA biomarkers in gastrointestinal disease. Clin Chim Acta 2025; 569:120182. [PMID: 39920958 DOI: 10.1016/j.cca.2025.120182] [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: 12/26/2024] [Revised: 01/31/2025] [Accepted: 02/02/2025] [Indexed: 02/10/2025]
Abstract
Detection and diagnosis of neoplastic and inflammatory gastrointestinal (GI) diseases are typically based on endoscopic and pathologic examination. In GI neoplastic diseases, diagnosis can be delayed due to the expense and invasive nature of this approach. Recently, PIWI-interacting RNAs (piRNAs), a group of small non-coding RNA molecules containing 24-31 nucleotides, have been thought to serve as biomarkers in many disease processes. For example, piRNAs are differentially expressed in GI cancer but their biologic role remains unclear. Using next-generation sequencing and microarray analyses, researchers have suggested that monitoring piRNAs could facilitate diagnosis and prognosis in GI disease. Herein, we reviewed the use of piRNAs in neoplastic, inflammatory, functional, and other diseases of the digestive system, which could shed new light on cancer screening, early detection, and personalized treatment.
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Affiliation(s)
- Xin-Yi Huang
- Department of Gastrointestinal Endoscopy, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China.
| | - Shu-Xian Chen
- Department of Gastrointestinal Endoscopy, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China.
| | - Zhen-Yu Wang
- Department of Gastrointestinal Endoscopy, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China.
| | - Yong-Sheng Lu
- Department of Gastrointestinal Endoscopy, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China.
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, Esophageal Cancer Prevention and Control Research Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China.
| | - Su-Zuan Chen
- Department of Gastrointestinal Endoscopy, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China.
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Xiong Y, Liu YF, Yang ZH, Huang CG. Impact of miRNAs involved in the STAT3 signaling pathway on esophageal cancer (Review). Oncol Rep 2025; 53:27. [PMID: 39749694 DOI: 10.3892/or.2024.8860] [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: 09/04/2024] [Accepted: 12/06/2024] [Indexed: 01/04/2025] Open
Abstract
Esophageal cancer (ESCA) is a common tumor noted in the digestive tract, which is highly malignant due to unclear early symptoms and poor last‑stage treatment effects; its mortality rate is relatively high. MicroRNA (miR) and signal transducer and activator of transcription 3 (STAT3) are key components of cellular signaling pathways; their interaction forms a complex and intricate information network that controls several types of biological behaviors in the cells. In the tumor cell, these signal transduction pathways are abnormally active, indicating that the STAT3 signaling pathway mediated by miRs is involved in the progression of various cancer types. The present review introduces the biological characteristics of miR and STAT3 and their relationship with ESCA. It summarizes the regulation of ESCA by the miR and STAT3 signaling pathways and analyzes the effects of these pathways on proliferation, apoptosis, invasion, metastasis and immune escape of cancer cells, as well as the impact on patient survival and prognosis. The purpose of the present review is to assess the miR/STAT3 signaling pathway in ESCA, improve the understanding of the pathogenesis of ESCA and facilitate the identification of therapeutic targets for ESCA.
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Affiliation(s)
- Ying Xiong
- School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Yi-Fan Liu
- School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Zhi-Hui Yang
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Cong-Gai Huang
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
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Mahmud M, Munjal A, Savani M, Win H, Rozell U, Arshad J. Biomarker Testing and Role of Tyrosine Kinase Inhibitors and Immunotherapy for Esophageal Squamous Cell Carcinoma. FOREGUT: THE JOURNAL OF THE AMERICAN FOREGUT SOCIETY 2024; 4:467-474. [DOI: 10.1177/26345161241238748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Esophageal squamous cell carcinoma (ESCC) constitutes an aggressive subset of esophageal cancers that portends a poor prognosis. Management of ESCC has been historically challenging due to the limited effective therapeutic options. Broadening our understanding of the molecular landscape and identifying reliable biomarkers are essential in early detection, monitoring disease response and advancing treatment strategies. Recently, immunotherapy and tyrosine kinase inhibitors have changed the treatment algorithm of ESCC. In this review, we explore the molecular landscape and biomarkers that can aid in the management of ESCC and discuss the role of immunotherapy and tyrosine kinase inhibitors in the treatment of ESCC.
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Affiliation(s)
| | | | - Malvi Savani
- University of Arizona Cancer Center, Tucson, AZ, USA
| | - Hninyee Win
- University of Arizona Cancer Center, Tucson, AZ, USA
| | | | - Junaid Arshad
- University of Arizona Cancer Center, Tucson, AZ, USA
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Cai XH, Zhao SQ, Zhang K, Liu WT. Progress in research of proteomics related to digestive system tumor markers. Shijie Huaren Xiaohua Zazhi 2024; 32:716-726. [DOI: 10.11569/wcjd.v32.i10.716] [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: 08/26/2024] [Revised: 09/26/2024] [Accepted: 10/21/2024] [Indexed: 10/28/2024] Open
Abstract
The incidence and mortality of digestive system tumors are high. Even though the number of methods for tumor diagnosis and treatment is increasing, most of these tumors still cannot be diagnosed early, and their prognosis is poor. The lack of effective biomarkers and therapeutic targets is the reason why they cannot be diagnosed early and treated effectively. With the continuous development of proteomics technology, proteomics has become increasingly valuable in exploring the mechanisms of tumorigenesis and searching for biomarkers and drug targets. This article reviews the application progress of proteomics technology in screening of biomarkers for digestive system tumors, with an aim to provide new ideas for early diagnosis, prognosis, and treatment of digestive system tumors.
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Affiliation(s)
- Xiao-Han Cai
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Si-Qi Zhao
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Kai Zhang
- School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Wen-Tian Liu
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
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Zhang WY, Chang YJ, Shi RH. Artificial intelligence enhances the management of esophageal squamous cell carcinoma in the precision oncology era. World J Gastroenterol 2024; 30:4267-4280. [PMID: 39492825 PMCID: PMC11525855 DOI: 10.3748/wjg.v30.i39.4267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 08/31/2024] [Accepted: 09/19/2024] [Indexed: 10/12/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer with a poor prognosis. Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients. With the advancement of artificial intelligence (AI) technology and the proliferation of medical digital information, AI has demonstrated promising sensitivity and accuracy in assisting precise detection, treatment decision-making, and prognosis assessment of ESCC. It has become a unique opportunity to enhance comprehensive clinical management of ESCC in the era of precision oncology. This review examines how AI is applied to the diagnosis, treatment, and prognosis assessment of ESCC in the era of precision oncology, and analyzes the challenges and potential opportunities that AI faces in clinical translation. Through insights into future prospects, it is hoped that this review will contribute to the real-world application of AI in future clinical settings, ultimately alleviating the disease burden caused by ESCC.
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Affiliation(s)
- Wan-Yue Zhang
- School of Medicine, Southeast University, Nanjing 221000, Jiangsu Province, China
| | - Yong-Jian Chang
- School of Cyber Science and Engineering, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Rui-Hua Shi
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
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He M, Qi Y, Zheng ZM, Sha M, Zhao X, Chen YR, Chen ZH, Qian RY, Yao J, Yang ZD. Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma. World J Gastrointest Oncol 2024; 16:4194-4208. [DOI: 10.4251/wjgo.v16.i10.4194] [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: 01/08/2024] [Revised: 06/09/2024] [Accepted: 06/28/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND The clinical effects and detailed roles of long non-coding RNA (LncRNA) steroid receptor RNA activator 1 (SRA1) in esophageal squamous cell carcinoma (ESCC) remain ambiguous. In the present study, the complementary sites between lncRNA SRA1, miRNA-363-5p, and phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.
AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.
METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired. SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction. Cell counting Kit-8 assay, transwell invasion assay, glycolysis assay, and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1. The t-test and the χ2 test were used for comparison between groups. Survival curve analysis was performed using the Kaplan-Meier method.
RESULTS SRA1 downregulation was identified in ESCC. ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression. The introduction of SRA1 inhibited cell proliferation, glucose uptake, and lactate production in ESCC. In vivo, the growth of ESCC was hindered by SRA1 overexpression. Then, SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p. Lastly, the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.
CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis. The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.
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Affiliation(s)
- Ming He
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Ye Qi
- Department of Nursing, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Ze-Mao Zheng
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Min Sha
- Institute of Clinical Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou 225300, Zhejiang Province, China
| | - Xiang Zhao
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Yu-Rao Chen
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Zheng-Hai Chen
- Department of Thoracic Surgery, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Rong-Yu Qian
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Juan Yao
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Zheng-Dong Yang
- Department of Thoracic Surgery, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
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12
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Chen Y, Ma Y, Wu H, Wei X, Xu Z, Wang Q. Examining the relationship between preoperative nutritional and symptom assessment and postoperative atrial fibrillation in esophageal squamous cell carcinoma patients: a retrospective cohort study. BMC Surg 2024; 24:298. [PMID: 39385162 PMCID: PMC11463059 DOI: 10.1186/s12893-024-02609-7] [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: 02/16/2024] [Accepted: 10/01/2024] [Indexed: 10/11/2024] Open
Abstract
OBJECTIVE The study aimed to examine the relationship between preoperative nutritional status, symptom burden, and the occurrence of postoperative atrial fibrillation in Esophageal Squamous Cell Carcinoma patients. METHODS The study, conducted in the Department of Thoracic Surgery at the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, applied the NRS 2002, SGA and MSAS scoring systems as measures of nutritional status and symptom occurrence in patients diagnosed with ESCC. Univariate and multivariate logistic regression analysis were performed to evaluate the association between nutritional scores, symptom scores, and postoperative complications. RESULTS The research found a significant correlation between high MSAS scores and postoperative atrial fibrillation. Patients with high symptom burden also tended to have nutritional risk or malnutrition according to the NRS2002 and SGA scores. CONCLUSION There is a need for healthcare providers to pay attention to ESCC patients' physical and psychological symptoms. Close monitoring of nutritional status and timely nutritional interventions should be integrated into these patients' care plans as they have been found to be related to postoperative complications such as atrial fibrillation.
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Affiliation(s)
- Yunyun Chen
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China
| | - Yan Ma
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China
| | - Haiyan Wu
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China
| | - Xinqi Wei
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China
| | - Zhiyun Xu
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China.
| | - Qingmei Wang
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China.
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Chen J, Liu X, Zhang Z, Su R, Geng Y, Guo Y, Zhang Y, Su M. Early Diagnostic Markers for Esophageal Squamous Cell Carcinoma: Copy Number Alteration Gene Identification and cfDNA Detection. J Transl Med 2024; 104:102127. [PMID: 39182610 DOI: 10.1016/j.labinv.2024.102127] [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: 05/25/2024] [Revised: 08/17/2024] [Accepted: 08/19/2024] [Indexed: 08/27/2024] Open
Abstract
The high mortality rate of esophageal squamous cell carcinoma (ESCC) is exacerbated by the absence of early diagnostic markers. The pronounced heterogeneity of mutations in ESCC renders copy number alterations (CNAs) more prevalent among patients. The identification of CNA genes within esophageal squamous dysplasia (ESD), a precancerous stage of ESCC, is crucial for advancing early detection efforts. Utilization of liquid biopsies via droplet-based digital PCR (ddPCR) offers a novel strategy for detecting incipient tumor traces. This study undertook a thorough investigation of CNA profiles across ESCC development stages, integrating data from existing databases and prior investigations to pinpoint and confirm CNA markers conducive to early detection of ESCC. Targeted sequencing was employed to select potential early detection genes, followed by the establishment of prediction models for ESCC early detection using ddPCR. Our analysis revealed widespread CNAs during the ESD stage, mirroring the CNA landscape observed in ESCC. A total of 40 CNA genes were identified as highly frequent in both ESCC and ESD lesions, through a comprehensive gene-level CNA analysis encompassing ESD and ESCC tissues, ESCC cell lines, and pan-cancer data sets. Subsequent validation of 5 candidate markers via ddPCR underscored the efficacy of combined predictive models encompassing PIK3CA, SOX2, EGFR, MYC, and CCND1 in early ESCC screening, as evidenced by the area-under-the-curve values exceeding 0.92 (P < .0001) across various detection contexts. The findings highlighted the significant utility of CNA genes in the early screening of ESCC, presenting robust models that could facilitate early detection, broad-scale population screening, and adjunctive diagnosis.
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Affiliation(s)
- Jiamin Chen
- Department of Pathology, Institute of Clinical Pathology, Shantou University Medical College, Shantou, China
| | - Xi Liu
- Department of Pathology, Institute of Clinical Pathology, Shantou University Medical College, Shantou, China
| | - Zhihua Zhang
- Department of Pathology, Institute of Clinical Pathology, Shantou University Medical College, Shantou, China
| | - Ruibing Su
- Department of Pathology, Institute of Clinical Pathology, Shantou University Medical College, Shantou, China; Department of Cardiology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Yiqun Geng
- Department of Molecular Pathology, Shantou University Medical College, Shantou, China
| | - Yi Guo
- Department of Endoscopy, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Yimin Zhang
- Clinical Research Center, Shantou Central Hospital, Shantou, China
| | - Min Su
- Department of Pathology, Institute of Clinical Pathology, Shantou University Medical College, Shantou, China.
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Tang Q, Wu S, Zhao B, Li Z, Zhou Q, Yu Y, Yang X, Wang R, Wang X, Wu W, Wang S. Reprogramming of glucose metabolism: The hallmark of malignant transformation and target for advanced diagnostics and treatments. Biomed Pharmacother 2024; 178:117257. [PMID: 39137648 DOI: 10.1016/j.biopha.2024.117257] [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: 06/11/2024] [Revised: 07/30/2024] [Accepted: 08/02/2024] [Indexed: 08/15/2024] Open
Abstract
Reprogramming of cancer metabolism has become increasingly concerned over the last decade, particularly the reprogramming of glucose metabolism, also known as the "Warburg effect". The reprogramming of glucose metabolism is considered a novel hallmark of human cancers. A growing number of studies have shown that reprogramming of glucose metabolism can regulate many biological processes of cancers, including carcinogenesis, progression, metastasis, and drug resistance. In this review, we summarize the major biological functions, clinical significance, potential targets and signaling pathways of glucose metabolic reprogramming in human cancers. Moreover, the applications of natural products and small molecule inhibitors targeting glucose metabolic reprogramming are analyzed, some clinical agents targeting glucose metabolic reprogramming and trial statuses are summarized, as well as the pros and cons of targeting glucose metabolic reprogramming for cancer therapy are analyzed. Overall, the reprogramming of glucose metabolism plays an important role in the prediction, prevention, diagnosis and treatment of human cancers. Glucose metabolic reprogramming-related targets have great potential to serve as biomarkers for improving individual outcomes and prognosis in cancer patients. The clinical innovations related to targeting the reprogramming of glucose metabolism will be a hotspot for cancer therapy research in the future. We suggest that more high-quality clinical trials with more abundant drug formulations and toxicology experiments would be beneficial for the development and clinical application of drugs targeting reprogramming of glucose metabolism.This review will provide the researchers with the broader perspective and comprehensive understanding about the important significance of glucose metabolic reprogramming in human cancers.
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Affiliation(s)
- Qing Tang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China.
| | - Siqi Wu
- The First Clinical School of Guangzhou University of Chinese Medicine；Department of Oncology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510000, China; Zhongshan Institute for Drug Discovery, SIMM, CAS, Zhongshan 528400, China
| | - Baiming Zhao
- The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Department of Traditional Chinese Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Zhanyang Li
- School of Biosciences and Biopharmaceutics, Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Qichun Zhou
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Yaya Yu
- The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Xiaobing Yang
- The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Rui Wang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Xi Wang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Wanyin Wu
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China.
| | - Sumei Wang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China.
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Talukdar J, Malik A, Kataki K, Choudhury BN, Baruah MN, Bhattacharyya M, Sarma MP, Bhattacharjee M, Basak M, Kashyap MP, Bhattacharjee S, Ali E, Keppen C, Kalita S, Kalita MJ, Das PP, Hazarika G, Deka AJ, Dutta K, Idris MG, Akhtar S, Medhi S. Expression of Interleukin-8, Interleukin-12 and Interleukin-13 in Esophageal Squamous Cell Carcinoma: Biomarker Potentiality and Prognostic Significance. J Gastrointest Cancer 2024; 55:1239-1255. [PMID: 38910194 DOI: 10.1007/s12029-024-01063-1] [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] [Accepted: 04/27/2024] [Indexed: 06/25/2024]
Abstract
PURPOSE Interleukin-8 (IL8), Interleukin-12 (IL12) and Interleukin-13 (IL13) are cytokines that play regulatory role in cancer pathogenesis. We analysed their expression profile to evaluate as molecular biomarkers of esophageal squamous cell carcinoma (ESCC) and their association with different parameters and patient survival. METHODS Expression analysis was performed by Real time quantitative polymerase chain reaction and receiver operating characteristic (ROC) curve analysis was done. The expression profiles were associated with different clinicopathological and dietary factors. Survival and hazard analysis were also performed. RESULTS IL8 expression showed upregulation in tissue (p = 0.000) and blood samples (p = 0.481), IL12 expression showed downregulation in tissue samples (p = 0.064) and upregulation in blood samples (p = 0.689) and IL13 expression showed upregulation in tissue (p = 0.000) and blood samples (p = 0.006). IL13 expression in tissue showed the highest area under the curve (AUC) value (0.773) for ESCC diagnosis, followed by IL8 expression in tissue (0.704) and IL13 expression in blood (0.643). This study also reveals the correlation of studied cytokines in tissue and blood level. Different clinicopathological and dietary factors showed significant association (p < 0.05) with IL8, IL12 and IL13 expression and with survival of ESCC patients. IL8 expression in blood and IL12 expression in tissue and blood showed significant association (p < 0.05) with patient survival. CONCLUSION Altered expression of IL8, IL12 and IL13 may be associated with ESCC progression. Overexpression of IL8 and IL13 in tissue samples may be potential biomarkers for ESCC screening. Additionally, both survival and hazard analysis data indicate the effects of different parameters on the prognosis of ESCC patients.
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Affiliation(s)
- Jayasree Talukdar
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India
| | - Abdul Malik
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Kangkana Kataki
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India
| | | | - Munindra Narayan Baruah
- Department of Head and Neck Oncology, North East Cancer Hospital and Research Institute, Jorabat, Assam, India
| | - Mallika Bhattacharyya
- Department of Gastroentrology, Gauhati Medical College and Hospital, Guwahati, Assam, India
| | - Manash Pratim Sarma
- Program of Biotechnology, Faculty of Science, Assam down town University, Guwahati, Assam, India
| | - Minakshi Bhattacharjee
- Program of Biotechnology, Faculty of Science, Assam down town University, Guwahati, Assam, India
| | - Mrinmoy Basak
- Faculty of Pharmaceutical Sciences, Assam down town University, Guwahati, Assam, India
| | - Manash Pratim Kashyap
- Program of Statistics, Faculty of Science, Assam down town University, Guwahati, Assam, India
| | | | - Eyashin Ali
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India
| | - Chenole Keppen
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India
| | - Simanta Kalita
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India
- Multidisciplinary Research Unit, Diphu Medical College and Hospital, Karbi Anglong, Assam, India
| | - Manash Jyoti Kalita
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India
| | - Partha Pratim Das
- Multidisciplinary Research Unit, Fakhruddin Ali Ahmed Medical College and Hospital, Barpeta, Assam, India
| | - Gautam Hazarika
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India
| | - Ankur Jyoti Deka
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India
| | - Kalpajit Dutta
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India
| | | | - Suhail Akhtar
- A. T. Still University of Health Sciences, Kirksville, MO, USA
| | - Subhash Medhi
- Department of Bioengineering and Technology, Gauhati University, Gawahati, Assam, India.
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Pubu S, Zhang JW, Yang J. Early diagnosis of esophageal cancer: How to put "early detection" into effect? World J Gastrointest Oncol 2024; 16:3386-3392. [PMID: 39171169 PMCID: PMC11334019 DOI: 10.4251/wjgo.v16.i8.3386] [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: 03/19/2024] [Revised: 05/04/2024] [Accepted: 05/20/2024] [Indexed: 08/07/2024] Open
Abstract
This editorial comments on the article by Qu et al in a recent edition of World Journal of Gastrointestinal Oncology, focusing on the importance of early diagnosis in managing esophageal cancer and strategies for achieving "early detection". The five-year age-standardized net survival for esophageal cancer patients falls short of expectations. Early detection and accurate diagnosis are critical strategies for improving the treatment outcomes of esophageal cancer. While advancements in endoscopic technology have been significant, there seems to be an excessive emphasis on the latest high-end endoscopic devices and various endoscopic resection techniques. Therefore, it is imperative to redirect focus towards proactive early detection strategies for esophageal cancer, investigate the most cost-effective screening methods suitable for different regions, and persistently explore practical solutions to improve the five-year survival rate of patients with esophageal cancer.
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Affiliation(s)
- Suolang Pubu
- Department of Gastroenterology, Changdu People’s Hospital of Xizang, Changdu 854000, Tibet Autonomous Region, China
| | - Jun-Wen Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jian Yang
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
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Pubu S, Zhang JW, Yang J. Early diagnosis of esophageal cancer: How to put "early detection" into effect? World J Gastrointest Oncol 2024; 16:3386-3392. [PMID: 39171169 DOI: 10.4251/wjgo.v16.i8.3386if:] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/04/2024] [Accepted: 05/20/2024] [Indexed: 03/07/2025] Open
Abstract
This editorial comments on the article by Qu et al in a recent edition of World Journal of Gastrointestinal Oncology, focusing on the importance of early diagnosis in managing esophageal cancer and strategies for achieving "early detection". The five-year age-standardized net survival for esophageal cancer patients falls short of expectations. Early detection and accurate diagnosis are critical strategies for improving the treatment outcomes of esophageal cancer. While advancements in endoscopic technology have been significant, there seems to be an excessive emphasis on the latest high-end endoscopic devices and various endoscopic resection techniques. Therefore, it is imperative to redirect focus towards proactive early detection strategies for esophageal cancer, investigate the most cost-effective screening methods suitable for different regions, and persistently explore practical solutions to improve the five-year survival rate of patients with esophageal cancer.
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Affiliation(s)
- Suolang Pubu
- Department of Gastroenterology, Changdu People's Hospital of Xizang, Changdu 854000, Tibet Autonomous Region, China
| | - Jun-Wen Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jian Yang
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
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Zhang Y, Li Y, Fang T, Zhong X, Yuan P, Wang M, Lu W, Liu J, Zhang L. Analysis of spiritual well-being status and influencing factors in patients with esophageal cancer: a cross-sectional study. Support Care Cancer 2024; 32:555. [PMID: 39066833 DOI: 10.1007/s00520-024-08760-4] [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: 02/26/2024] [Accepted: 07/22/2024] [Indexed: 07/30/2024]
Abstract
OBJECTIVE To understand the status of spiritual well-being in patients with esophageal cancer and analyze its influencing factors. METHODS A total of 187 patients with esophageal cancer (EC) from two grade A hospitals in Chengdu were selected and investigated by general data questionnaire, chronic disease function evaluation-spirituality scale 12 (FACIT-SP-12), general well-being scale (GWB), and Anderson symptom assessment scale gastrointestinal tract (MDASI-GI). RESULTS The spiritual well-being score of patients with esophageal cancer was (25.13 ± 9.63). Spiritual well-being was positively correlated with general well-being and negatively correlated with symptom burden (P < 0.01). The results of multiple stepwise linear regression analysis showed that hobbies, disease stage, general well-being, and symptom burden were the main influencing factors for the spiritual well-being of esophageal cancer patients (P < 0.05), explaining 49.0% of the total variation. CONCLUSIONS The spiritual well-being of patients with esophageal cancer is lower than the middle level, In addition, whether there is a hobby in life, disease stage, subjective well-being, and symptom burden are the main factors affecting the spiritual well-being of patients with EC. It is suggested that medical staff should take targeted care measures according to the influencing factors, so as to improve the spiritual well-being level of patients and improve the quality of life of patients.
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Affiliation(s)
- Yiying Zhang
- School of Nursing, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Yanjia Li
- Sichuan Taikang Hospital, Chengdu, 610213, Sichuan, China
| | - Ting Fang
- School of Nursing, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Xiaoying Zhong
- School of Nursing, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Ping Yuan
- School of Nursing, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Meng Wang
- School of Nursing, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Weinan Lu
- School of Nursing, Chengdu Medical College, Chengdu, 610500, Sichuan, China
- The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Jing Liu
- School of Nursing, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Limei Zhang
- School of Nursing, Chengdu Medical College, Chengdu, 610500, Sichuan, China.
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19
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Khan IR, Sadida HQ, Hashem S, Singh M, Macha MA, Al-Shabeeb Akil AS, Khurshid I, Bhat AA. Therapeutic implications of signaling pathways and tumor microenvironment interactions in esophageal cancer. Biomed Pharmacother 2024; 176:116873. [PMID: 38843587 DOI: 10.1016/j.biopha.2024.116873] [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: 03/24/2024] [Revised: 05/21/2024] [Accepted: 06/03/2024] [Indexed: 06/20/2024] Open
Abstract
Esophageal cancer (EC) is significantly influenced by the tumor microenvironment (TME) and altered signaling pathways. Downregulating these pathways in EC is essential for suppressing tumor development, preventing metastasis, and enhancing therapeutic outcomes. This approach can increase tumor sensitivity to treatments, enhance patient outcomes, and inhibit cancer cell proliferation and spread. The TME, comprising cellular and non-cellular elements surrounding the tumor, significantly influences EC's development, course, and treatment responsiveness. Understanding the complex relationships within the TME is crucial for developing successful EC treatments. Immunotherapy is a vital TME treatment for EC. However, the heterogeneity within the TME limits the application of anticancer drugs outside clinical settings. Therefore, identifying reliable microenvironmental biomarkers that can detect therapeutic responses before initiating therapy is crucial. Combining approaches focusing on EC signaling pathways with TME can enhance treatment outcomes. This integrated strategy aims to interfere with essential signaling pathways promoting cancer spread while disrupting factors encouraging tumor development. Unraveling aberrant signaling pathways and TME components can lead to more focused and efficient treatment approaches, identifying specific cellular targets for treatments. Targeting the TME and signaling pathways may reduce metastasis risk by interfering with mechanisms facilitating cancer cell invasion and dissemination. In conclusion, this integrative strategy has significant potential for improving patient outcomes and advancing EC research and therapy. This review discusses the altered signaling pathways and TME in EC, focusing on potential future therapeutics.
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Affiliation(s)
- Inamu Rashid Khan
- Department of Zoology, Central University of Kashmir, Ganderbal, Jammu and Kashmir 191201, India
| | - Hana Q Sadida
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha 26999, Qatar
| | - Sheema Hashem
- Department of Human Genetics, Sidra Medicine Doha 26999, Qatar
| | - Mayank Singh
- Department of Medical Oncology (Lab), Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Muzafar A Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Jammu and Kashmir 192122, India
| | - Ammira S Al-Shabeeb Akil
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha 26999, Qatar
| | - Ibraq Khurshid
- Department of Zoology, Central University of Kashmir, Ganderbal, Jammu and Kashmir 191201, India.
| | - Ajaz A Bhat
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha 26999, Qatar.
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20
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Chou CK, Karmakar R, Tsao YM, Jie LW, Mukundan A, Huang CW, Chen TH, Ko CY, Wang HC. Evaluation of Spectrum-Aided Visual Enhancer (SAVE) in Esophageal Cancer Detection Using YOLO Frameworks. Diagnostics (Basel) 2024; 14:1129. [PMID: 38893655 PMCID: PMC11171540 DOI: 10.3390/diagnostics14111129] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 05/16/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024] Open
Abstract
The early detection of esophageal cancer presents a substantial difficulty, which contributes to its status as a primary cause of cancer-related fatalities. This study used You Only Look Once (YOLO) frameworks, specifically YOLOv5 and YOLOv8, to predict and detect early-stage EC by using a dataset sourced from the Division of Gastroenterology and Hepatology, Ditmanson Medical Foundation, Chia-Yi Christian Hospital. The dataset comprised 2741 white-light images (WLI) and 2741 hyperspectral narrowband images (HSI-NBI). They were divided into 60% training, 20% validation, and 20% test sets to facilitate robust detection. The images were produced using a conversion method called the spectrum-aided vision enhancer (SAVE). This algorithm can transform a WLI into an NBI without requiring a spectrometer or spectral head. The main goal was to identify dysplasia and squamous cell carcinoma (SCC). The model's performance was evaluated using five essential metrics: precision, recall, F1-score, mAP, and the confusion matrix. The experimental results demonstrated that the HSI model exhibited improved learning capabilities for SCC characteristics compared with the original RGB images. Within the YOLO framework, YOLOv5 outperformed YOLOv8, indicating that YOLOv5's design possessed superior feature-learning skills. The YOLOv5 model, when used in conjunction with HSI-NBI, demonstrated the best performance. It achieved a precision rate of 85.1% (CI95: 83.2-87.0%, p < 0.01) in diagnosing SCC and an F1-score of 52.5% (CI95: 50.1-54.9%, p < 0.01) in detecting dysplasia. The results of these figures were much better than those of YOLOv8. YOLOv8 achieved a precision rate of 81.7% (CI95: 79.6-83.8%, p < 0.01) and an F1-score of 49.4% (CI95: 47.0-51.8%, p < 0.05). The YOLOv5 model with HSI demonstrated greater performance than other models in multiple scenarios. This difference was statistically significant, suggesting that the YOLOv5 model with HSI significantly improved detection capabilities.
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Affiliation(s)
- Chu-Kuang Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan;
- Obesity Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan
- Department of Medical Quality, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan
| | - Riya Karmakar
- Department of Mechanical Engineering, National Chung Cheng University, Chia-Yi 62102, Taiwan; (R.K.); (Y.-M.T.); (A.M.)
| | - Yu-Ming Tsao
- Department of Mechanical Engineering, National Chung Cheng University, Chia-Yi 62102, Taiwan; (R.K.); (Y.-M.T.); (A.M.)
| | - Lim Wei Jie
- Department of Computer Science, Multimedia University (Cyberjaya), Persiaran Multimedia, Cyberjaya 63100, Malaysia;
| | - Arvind Mukundan
- Department of Mechanical Engineering, National Chung Cheng University, Chia-Yi 62102, Taiwan; (R.K.); (Y.-M.T.); (A.M.)
| | - Chien-Wei Huang
- Department of Gastroenterology, Kaohsiung Armed Forces General Hospital, 2, Zhongzheng 1st. Rd., Lingya District, Kaohsiung City 80284, Taiwan;
- Department of Nursing, Tajen University, 20, Weixin Rd., Yanpu Township 90741, Pingtung County, Taiwan
| | - Tsung-Hsien Chen
- Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan;
| | - Chau-Yuan Ko
- Department of Gastroenterology, Kaohsiung Armed Forces General Hospital, 2, Zhongzheng 1st. Rd., Lingya District, Kaohsiung City 80284, Taiwan;
| | - Hsiang-Chen Wang
- Department of Mechanical Engineering, National Chung Cheng University, Chia-Yi 62102, Taiwan; (R.K.); (Y.-M.T.); (A.M.)
- Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chia-Yi 62247, Taiwan
- Director of Technology Development, Hitspectra Intelligent Technology Co., Ltd., Kaohsiung City 80661, Taiwan
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21
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Zhao YX, Zhao HP, Zhao MY, Yu Y, Qi X, Wang JH, Lv J. Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:2638-2656. [PMID: 38855150 PMCID: PMC11154680 DOI: 10.3748/wjg.v30.i20.2638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/26/2024] [Accepted: 05/13/2024] [Indexed: 05/27/2024] Open
Abstract
As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.
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Affiliation(s)
- Yi-Xin Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Meng-Yao Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Yan Yu
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Xi Qi
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Ji-Han Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, Shaanxi Province, China
| | - Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
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22
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Qi JH, Huang SL, Jin SZ. Novel milestones for early esophageal carcinoma: From bench to bed. World J Gastrointest Oncol 2024; 16:1104-1118. [PMID: 38660637 PMCID: PMC11037034 DOI: 10.4251/wjgo.v16.i4.1104] [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: 12/15/2023] [Revised: 01/28/2024] [Accepted: 02/26/2024] [Indexed: 04/10/2024] Open
Abstract
Esophageal cancer (EC) is the seventh most common cancer worldwide, and esophageal squamous cell carcinoma (ESCC) accounts for the majority of cases of EC. To effectively diagnose and treat ESCC and improve patient prognosis, timely diagnosis in the initial phase of the illness is necessary. This article offers a detailed summary of the latest advancements and emerging technologies in the timely identification of ECs. Molecular biology and epigenetics approaches involve the use of molecular mechanisms combined with fluorescence quantitative polymerase chain reaction (qPCR), high-throughput sequencing technology (next-generation sequencing), and digital PCR technology to study endogenous or exogenous biomolecular changes in the human body and provide a decision-making basis for the diagnosis, treatment, and prognosis of diseases. The investigation of the microbiome is a swiftly progressing area in human cancer research, and microorganisms with complex functions are potential components of the tumor microenvironment. The intratumoral microbiota was also found to be connected to tumor progression. The application of endoscopy as a crucial technique for the early identification of ESCC has been essential, and with ongoing advancements in technology, endoscopy has continuously improved. With the advancement of artificial intelligence (AI) technology, the utilization of AI in the detection of gastrointestinal tumors has become increasingly prevalent. The implementation of AI can effectively resolve the discrepancies among observers, improve the detection rate, assist in predicting the depth of invasion and differentiation status, guide the pericancerous margins, and aid in a more accurate diagnosis of ESCC.
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Affiliation(s)
- Ji-Han Qi
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Shi-Ling Huang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Shi-Zhu Jin
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
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23
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Mi Y, Chen L, Wang C, Miao Y, Song C, Su J, Wang L. AURKA knockdown inhibits esophageal squamous cell carcinoma progression through ferroptosis. Heliyon 2024; 10:e28365. [PMID: 38571661 PMCID: PMC10987997 DOI: 10.1016/j.heliyon.2024.e28365] [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: 11/06/2023] [Revised: 03/18/2024] [Accepted: 03/18/2024] [Indexed: 04/05/2024] Open
Abstract
Aurora kinase A, as a pro-carcinogenic in gastric cancer and glioma kinase, is enhanced in several human tumors. However, it's regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. Thus, this study aimed to investigate the expression status, functional roles, and molecular mechanisms of AURKA in ESCC development. AURKA expression was analyzed by the screening of the GEO database and detected using an immunohistochemical method. The biological function of AURKA on ESCC was evaluated in vitro and in vivo. Western blot assay, malondialdehyde (MDA), iron, and glutathione (GSH) kits were utilized to assess changes in ferroptosis. Database analysis results showed that AURKA was a differential gene in ESCC and was highly expressed in human ESCC tissues. Functionally, AURKA knockdown decreased ESCC cell proliferation, invasion, and metastasis both in vitro and in vivo. Moreover, when AURKA was knockdown, cells were more correctly blocked in the G2/M phase, and the ferroptosis-related MDA and Fe increased, whereas the GSH reduced. Consistently, Glutathione peroxidase 4 (GPX4) and solute carrier family 7a member 11 (SLC7A11) expression were downregulated by AURKA knockdown. However, ferroptosis inhibitor partially restore ESCC cell proliferation, invasion, and metastasis caused by AURKA knockdown. AURKA knockdown enhances ferroptosis and acts against cancer progression in ESCC. AURKA acts as a tumor-promoting gene and may serve as potential target for ESCC treatment.
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Affiliation(s)
- Yuan Mi
- Department of Emergency, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
| | - Liying Chen
- Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, Hebei, China
| | - Cong Wang
- Department of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, Hebei, China
| | - Yuxin Miao
- Department of Physiology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China
| | - Chuntao Song
- Department of Emergency, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
| | - Jie Su
- Department of Emergency, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
| | - Lei Wang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
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24
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Romanowicz A, Lukaszewicz-Zajac M, Mroczko B. Exploring Potential Biomarkers in Oesophageal Cancer: A Comprehensive Analysis. Int J Mol Sci 2024; 25:4253. [PMID: 38673838 PMCID: PMC11050399 DOI: 10.3390/ijms25084253] [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: 03/05/2024] [Revised: 04/04/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Oesophageal cancer (OC) is the sixth leading cause of cancer-related death worldwide. OC is highly aggressive, primarily due to its late stage of diagnosis and poor prognosis for patients' survival. Therefore, the establishment of new biomarkers that will be measured with non-invasive techniques at low cost is a critical issue in improving the diagnosis of OC. In this review, we summarize several original studies concerning the potential significance of selected chemokines and their receptors, including inflammatory proteins such as interleukin-6 (IL-6) and C-reactive protein (CRP), hematopoietic growth factors (HGFs), claudins (CLDNs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), adamalysines (ADAMs), as well as DNA- and RNA-based biomarkers, in OC. The presented results indicate the significant correlation between the CXCL12, CXCR4, CXCL8/CXCR2, M-CSF, MMP-2, MMP-9 ADAM17, ADAMTS-6, and CLDN7 levels and tumor stage, as well as the clinicopathological parameters of OC, such as the presence of lymph node and/or distant metastases. CXCL12, CXCL8/CXCR2, IL-6, TIMP-2, ADAM9, and ADAMTS-6 were prognostic factors for the overall survival of OC patients. Furthermore, IL-6, CXCR4, CXCL8, and MMP-9 indicate higher diagnostic utility based on the area under the ROC curve (AUC) than well-established OC tumor markers, whereas CLDN18.2 can be used in novel targeted therapies for OC patients.
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Affiliation(s)
- Adrianna Romanowicz
- Department of Biochemical Diagnostics, Medical University of Bialystok, ul. Waszyngtona 15a, 15-269 Bialystok, Poland; (A.R.); (B.M.)
| | - Marta Lukaszewicz-Zajac
- Department of Biochemical Diagnostics, Medical University of Bialystok, ul. Waszyngtona 15a, 15-269 Bialystok, Poland; (A.R.); (B.M.)
| | - Barbara Mroczko
- Department of Biochemical Diagnostics, Medical University of Bialystok, ul. Waszyngtona 15a, 15-269 Bialystok, Poland; (A.R.); (B.M.)
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, ul. Waszyngtona 15a, 15-269 Bialystok, Poland
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25
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Seto N, Miura K, Jin L, Nakahara M. A Case of Esophageal Cancer With Markedly Elevated Soluble Interleukin-2 Receptor: A Potential of Soluble Interleukin-2 Receptor as a Biomarker. Cureus 2024; 16:e57477. [PMID: 38699096 PMCID: PMC11065481 DOI: 10.7759/cureus.57477] [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] [Accepted: 04/01/2024] [Indexed: 05/05/2024] Open
Abstract
We report an autopsy case of advanced esophageal cancer with multiple metastases that presented with a markedly high level of sIL-2R. An 83-year-old man was admitted to our hospital with a 1-week history of epigastric distress, appetite loss, and fatigue. Imaging examinations revealed a large liver tumor. Although the tumor markers for gastrointestinal and liver cancers were within normal limits, the sIL-2R level was extremely high (10,384 U/mL). The patient died immediately after admission due to the rapid course of the disease. An autopsy showed advanced esophageal cancer with multiple metastases, including the liver, lungs, and multiple lymph nodes. In histological examinations, esophageal cancer was a mixture of well- and poorly differentiated squamous cell carcinoma, in which poorly differentiated cancer cells expressed sIL-2R on immunohistochemical staining. However, we failed to detect positive staining for sIL-2R in the lymphocytes. Our findings revealed that solid tumors could express sIL-2R. Although sIL-2R is a tumor marker used for hematological malignancies, such as malignant lymphoma, this case report highlights the value of the measurement of sIL-2R levels in advanced solid tumors, including esophageal cancer. We concluded that sIL-2R has potential as a biomarker in advanced solid tumors for cancer staging and treatment response.
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Affiliation(s)
- Nayuta Seto
- Department of Internal Medicine, Chichibu Municipal Hospital, Saitama, JPN
| | - Kouichi Miura
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi, JPN
| | - Ling Jin
- Department of Pathology, Saitama Medical University, Saitama, JPN
| | - Moriyasu Nakahara
- Department of Gastroenterology, Chichibu Municipal Hospital, Saitama, JPN
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26
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Mou X, Peng Z, Yin T, Sun X. Non-endoscopic Screening for Esophageal Squamous Cell Carcinoma: Recent Advances. J Gastrointest Cancer 2024; 55:118-128. [PMID: 37924487 DOI: 10.1007/s12029-023-00980-x] [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] [Accepted: 10/19/2023] [Indexed: 11/06/2023]
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors in the gastrointestinal tract, and China has a high incidence area with a high burden on the disease. As early symptoms of ESCC are not obvious, the mortality rate is high, and it is often diagnosed in the intermediate and advanced stages. However, early screening and treatment may reduce morbidity and mortality. METHODS Screening methods are divided into endoscopic and non-endoscopic screening. RESULTS Endoscopic screening cannot be widely used because of its invasive nature and high cost. Currently, non-endoscopic screening consists primarily of tumor biomarkers and cytology, and tumor biomarkers including autoantibodies, circulating tumor cells, circulating tumor DNA, exosomes and serum metabolomics are more likely to be effective. But the efficiency of early diagnosis of esophageal cancer is low and the accuracy of screening needs to be improved. The aim of this study is to summarize advances in non-endoscopic esophageal cancer screening and strategies to provide a scientific basis and research idea for esophageal cancer prevention and control. CONCLUSIONS Non-endoscopic screening is better than endoscopic screening. And the application of tumor biomarkers is much better than other non-endoscopic screening methods.
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Affiliation(s)
- Xiao Mou
- School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China.
| | - Zhenglin Peng
- College of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
| | - Tao Yin
- College of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
- Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Xingwang Sun
- College of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
- Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
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27
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Zhang C, Guo Z, Jing Z. Prediction of Response to Chemoradiotherapy by Dynamic Changes of Circulating Exosome Levels in Patients with Esophageal Squamous Cell Carcinoma. Int J Nanomedicine 2024; 19:1351-1362. [PMID: 38352821 PMCID: PMC10863473 DOI: 10.2147/ijn.s440684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 02/01/2024] [Indexed: 02/16/2024] Open
Abstract
Background The exosomes-based liquid biopsy represents a prospective biomarker for tumor screening, prognosis prediction, and tumor regression. This study aimed to isolate circulating exosomes (CEs) from plasma of the esophageal squamous cell carcinoma (ESCC) patients who received chemoradiotherapy through exosome detection method via the ultrafast-isolation system (EXODUS) and investigated the association between the dynamic changes of CE levels and therapeutic effect. Methods We isolated and quantitatively analyzed CEs from plasma of locally advanced ESCC patients received chemoradiotherapy at 2 time points: baseline (pre-chemoradiotherapy) and 2 months after the chemoradiotherapy (post-chemoradiotherapy). We isolated exosomes from plasma by EXODUS platform and confirmed them through nanoparticle tracking analysis (NTA), transmission electron microscope (TEM), and Western blot. The associations of CE level with clinicopathological characteristics, tumor regression, and progression-free survival (PFS) were analyzed. Results The average diameter of CEs was 107.4±14.3 nm at baseline and 101.7±17.1 nm at post-chemoradiotherapy. The mean exosome concentration significantly decreased after chemoradiotherapy (7.3×1011 particles/mL vs 5.4×1011 particles/mL, P < 0.001). The patients with stage III-IVA and tumor length ≥5cm had obviously higher baseline CE levels. Dynamic changes in CE levels were successfully applied for evaluation of chemoradiotherapy response and PFS. Furthermore, through multivariate Cox regression analysis, it was revealed that dynamic changes of CE levels were an independent predictor of PFS in locally advanced ESCC patients who received chemoradiotherapy. Conclusion Here, we demonstrated EXODUS platform isolated and enriched CEs from plasma of ESCC patients with high-purity and high-yield. The EXODUS platform can facilitate liquid biopsy based on exosomes translation to the clinic. Baseline CE levels can reflect ESCC tumor burden. The dynamic changes of CE levels during chemoradiotherapy allow the prediction of treatment effect and PFS of ESCC patients, requiring further investigations in larger patient cohorts.
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Affiliation(s)
- Chuanfeng Zhang
- Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang, 310013, People’s Republic of China
| | - Zhen Guo
- Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang, 310013, People’s Republic of China
| | - Zhao Jing
- Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang, 310013, People’s Republic of China
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28
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Wang F, Luo M, Cheng Y. KLF5 promotes esophageal squamous cell cancer through the transcriptional activation of FGFBP1. Med Oncol 2023; 41:17. [PMID: 38087142 PMCID: PMC10716083 DOI: 10.1007/s12032-023-02244-x] [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: 03/28/2023] [Accepted: 06/19/2023] [Indexed: 12/18/2023]
Abstract
Krüpple-like factor 5 (KLF5) is a zinc-finger-containing transcription factor implicated in several human malignancies, but its potential regulatory mechanisms implicated in esophageal squamous cell carcinoma (ESCC) remain elusive. Here, we show that KLF5 is upregulated in ESCC, where its level was significantly associated with tumor differentiation and lymph node metastasis status. Upregulated KLF5 expression promoted the proliferation, migration, and invasion of ESCC cells. Reduced KLF5 showed the opposite effects. Mechanistically, KLF5 exerts its tumor promotion effect by up-regulating fibroblast growth factor binding protein 1 (FGF-BP1) and snail family transcriptional repressor 2 (SNAIL2). KLF5 binds to the promoter regions of FGF-BP1 and transcriptionally activates its expression. Our study indicated that KLF5 could promote esophageal squamous cell cancer proliferation, migration, and invasion by upregulating FGF-BP1/SNAIL2 signaling. Our work suggests that KLF5 might be a proto-oncogene in ESCC and implicated in ESCC metastasis.
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Affiliation(s)
- Fengyun Wang
- Department of Oncology, First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology, Baotou, Inner Mongolia, China
| | - Ming Luo
- Imaging Department, Third Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, China
| | - Yufeng Cheng
- Department of Radiotherapy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No.107, West Wenhua Road, Lixia District, Jinan, Shandong, China.
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Li T, Xia J, Yun H, Sun G, Shen Y, Wang P, Shi J, Wang K, Yang H, Ye H. A novel autoantibody signatures for enhanced clinical diagnosis of pancreatic ductal adenocarcinoma. Cancer Cell Int 2023; 23:273. [PMID: 37974212 PMCID: PMC10655307 DOI: 10.1186/s12935-023-03107-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Accepted: 10/25/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that requires precise diagnosis for effective treatment. However, the diagnostic value of carbohydrate antigen 19 - 9 (CA19-9) is limited. Therefore, this study aims to identify novel tumor-associated autoantibodies (TAAbs) for PDAC diagnosis. METHODS A three-phase strategy comprising discovery, test, and validation was implemented. HuProt™ Human Proteome Microarray v3.1 was used to screen potential TAAbs in 49 samples. Subsequently, the levels of potential TAAbs were evaluated in 477 samples via enzyme-linked immunosorbent assay (ELISA) in PDAC, benign pancreatic diseases (BPD), and normal control (NC), followed by the construction of a diagnostic model. RESULTS In the discovery phase, protein microarrays identified 167 candidate TAAbs. Based on bioinformatics analysis, fifteen tumor-associated antigens (TAAs) were selected for further validation using ELISA. Ten TAAbs exhibited differentially expressed in PDAC patients in the test phase (P < 0.05), with an area under the curve (AUC) ranging from 0.61 to 0.76. An immunodiagnostic model including three TAAbs (anti-HEXB, anti-TXLNA, anti-SLAMF6) was then developed, demonstrating AUCs of 0.81 (58.0% sensitivity, 86.0% specificity) and 0.78 (55.71% sensitivity, 87.14% specificity) for distinguishing PDAC from NC. Additionally, the model yielded AUCs of 0.80 (58.0% sensitivity, 86.25% specificity) and 0.83 (55.71% sensitivity, 100% specificity) for distinguishing PDAC from BPD in the test and validation phases, respectively. Notably, the combination of the immunodiagnostic model with CA19-9 resulted in an increased positive rate of PDAC to 92.91%. CONCLUSION The immunodiagnostic model may offer a novel serological detection method for PDAC diagnosis, providing valuable insights into the development of effective diagnostic biomarkers.
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Affiliation(s)
- Tiandong Li
- College of Public Health, Zhengzhou University, 450001, Zhengzhou, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, 450052, Zhengzhou, Henan Province, China
| | - Junfen Xia
- Office of Health Care, The Third Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan Province, China
| | - Huan Yun
- Zhengzhou University, 450001, Zhengzhou, Henan Province, China
| | - Guiying Sun
- College of Public Health, Zhengzhou University, 450001, Zhengzhou, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, 450052, Zhengzhou, Henan Province, China
| | - Yajing Shen
- College of Public Health, Zhengzhou University, 450001, Zhengzhou, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, 450052, Zhengzhou, Henan Province, China
| | - Peng Wang
- College of Public Health, Zhengzhou University, 450001, Zhengzhou, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, 450052, Zhengzhou, Henan Province, China
| | - Jianxiang Shi
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, 450052, Zhengzhou, Henan Province, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, 450052, Zhengzhou, Henan Province, China
| | - Keyan Wang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, 450052, Zhengzhou, Henan Province, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, 450052, Zhengzhou, Henan Province, China
| | - Hongwei Yang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan Province, China
| | - Hua Ye
- College of Public Health, Zhengzhou University, 450001, Zhengzhou, Henan Province, China.
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, 450052, Zhengzhou, Henan Province, China.
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Mostufa S, Rezaei B, Yari P, Xu K, Gómez-Pastora J, Sun J, Shi Z, Wu K. Giant Magnetoresistance Based Biosensors for Cancer Screening and Detection. ACS APPLIED BIO MATERIALS 2023; 6:4042-4059. [PMID: 37725557 DOI: 10.1021/acsabm.3c00592] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/21/2023]
Abstract
Early-stage screening of cancer is critical in preventing its development and therefore can improve the prognosis of the disease. One accurate and effective method of cancer screening is using high sensitivity biosensors to detect optically, chemically, or magnetically labeled cancer biomarkers. Among a wide range of biosensors, giant magnetoresistance (GMR) based devices offer high sensitivity, low background noise, robustness, and low cost. With state-of-the-art micro- and nanofabrication techniques, tens to hundreds of independently working GMR biosensors can be integrated into fingernail-sized chips for the simultaneous detection of multiple cancer biomarkers (i.e., multiplexed assay). Meanwhile, the miniaturization of GMR chips makes them able to be integrated into point-of-care (POC) devices. In this review, we first introduce three types of GMR biosensors in terms of their structures and physics, followed by a discussion on fabrication techniques for those sensors. In order to achieve target cancer biomarker detection, the GMR biosensor surface needs to be subjected to biological decoration. Thus, commonly used methods for surface functionalization are also reviewed. The robustness of GMR-based biosensors in cancer detection has been demonstrated by multiple research groups worldwide and we review some representative examples. At the end of this review, the challenges and future development prospects of GMR biosensor platforms are commented on. With all their benefits and opportunities, it can be foreseen that GMR biosensor platforms will transition from a promising candidate to a robust product for cancer screening in the near future.
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Affiliation(s)
- Shahriar Mostufa
- Department of Electrical and Computer Engineering, Texas Tech University, Lubbock, Texas 79409, United States
| | - Bahareh Rezaei
- Department of Electrical and Computer Engineering, Texas Tech University, Lubbock, Texas 79409, United States
| | - Parsa Yari
- Department of Electrical and Computer Engineering, Texas Tech University, Lubbock, Texas 79409, United States
| | - Kanglin Xu
- Department of Computer Science, Texas Tech University, Lubbock, Texas 79409, United States
| | - Jenifer Gómez-Pastora
- Department of Chemical Engineering, Texas Tech University, Lubbock, Texas 79409, United States
| | - Jiajia Sun
- State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an, Shaanxi Province 710049, China
| | - Zongqian Shi
- State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an, Shaanxi Province 710049, China
| | - Kai Wu
- Department of Electrical and Computer Engineering, Texas Tech University, Lubbock, Texas 79409, United States
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Chiang H, Hughes M, Chang W. The role of microbiota in esophageal squamous cell carcinoma: A review of the literature. Thorac Cancer 2023; 14:2821-2829. [PMID: 37675608 PMCID: PMC10542467 DOI: 10.1111/1759-7714.15096] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 08/23/2023] [Indexed: 09/08/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) exhibits high incidence with poor prognosis. Alcohol drinking, cigarette smoking, and betel nut chewing are well-known risk factors. Dysbiosis, an imbalance of the microbiota residing in a local environment, is known to be associated with human diseases, especially cancer. This article reviews the current evidence of esophageal microbiota in ESCC carcinogenesis, including initiation, progression, and drug resistance. Articles involving the esophageal microbiota, diagnosis, treatment, and the progression of esophageal cancer were acquired using a comprehensive literature search in PubMed in recent 10 years. Based on 16S rRNA sequencing of human samples, cell, and animal studies, current evidence suggests dysbiosis of the esophagus promotes ESCC progression and chemotherapy resistance, leading to a poor prognosis. Smoking and drinking are associated with esophageal dysbiosis. Specific bacteria have been reported to promote carcinogenesis, involving either progression or drug resistance in ESCC, for example Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria promote ESCC cell proliferation and migration via the TLR4/NF-κB and IL-6/STAT3 pathways. F. nucleatum induces cisplatin resistance via the enrichment of immunosuppressive myeloid-derived suppressor cells (MDSCs). Correcting the dysbiosis and reducing the abundance of specific esophageal pathogens may help in suppressing cancer progression. In conclusion, esophageal dysbiosis is associated with ESCC progression and chemoresistance. Screening the oral and esophageal microbiota is a potential diagnostic tool for predicting ESCC development or drug-resistance. Repairing esophageal dysbiosis is a novel treatment for ESCC. Clinical trials with probiotics in addition to current chemotherapy are warranted to study the therapeutic effects.
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Affiliation(s)
- Hsueh‐Chien Chiang
- Department of Internal MedicineNational Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityTainanTaiwan
- Institute of Clinical Medicine, College of MedicineNational Cheng Kung UniversityTainanTaiwan
| | - Michael Hughes
- Institute of Clinical Medicine, College of MedicineNational Cheng Kung UniversityTainanTaiwan
- International Center for Wound Repair and Regeneration (iWRR), College of MedicineNational Cheng Kung UniversityTainanTaiwan
- Department of Life SciencesNational Cheng Kung UniversityTainanTaiwan
| | - Wei‐Lun Chang
- Department of Internal MedicineNational Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityTainanTaiwan
- Institute of Clinical Medicine, College of MedicineNational Cheng Kung UniversityTainanTaiwan
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Zheng X, Liu W, Zhu Y, Kong W, Su X, Huang L, Cui Y, Sun G. Development and Validation of the Oxidative Stress Related lncRNAs for Prognosis in Esophageal Squamous Cell Carcinoma. Cancers (Basel) 2023; 15:4399. [PMID: 37686677 PMCID: PMC10487246 DOI: 10.3390/cancers15174399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/20/2023] [Accepted: 08/31/2023] [Indexed: 09/10/2023] Open
Abstract
Esophageal squamous cell cancer (ESCC) is an aggressive disease associated with a poor prognosis. Long non-coding RNAs (lncRNAs) and oxidative stress play crucial roles in tumor progression. We aimed to identify an oxidative stress-related lncRNA signature that could predict the prognosis in ESCC. In the GSE53625 dataset, we identified 332 differentially expressed lncRNAs (DElncRNAs) between ESCC and control samples, out of which 174 were oxidative stress-related DElncRNAs. Subsequently, seven oxidative stress-related DElncRNAs (CCR5AS, LINC01749, PCDH9-AS1, TMEM220-AS1, KCNMA1-AS1, SNHG1, LINC01672) were selected based on univariate and LASSO Cox to build a prognostic risk model, and their expression was detected by RT-qPCR. The model exhibited an excellent ability for the prediction of overall survival (OS) and other clinicopathological traits using Kaplan-Meier (K-M) survival curves, receiver operating characteristic (ROC) curves, and the Wilcoxon test. Additionally, analysis of infiltrated immune cells and immune checkpoints indicated differences in immune status between the two risk groups. Finally, the in vitro experiments showed that PCDH9-AS1 overexpression inhibited proliferation ability and promoted apoptosis and oxidative stress levels in ESCC cells. In conclusion, our study demonstrated that a novel oxidative stress-related DElncRNA prognostic model performed favorably in predicting ESCC patient prognosis and benefits personalized clinical applications.
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Affiliation(s)
- Xuan Zheng
- School of Public Health, North China University of Science and Technology, Tangshan 063200, China; (X.Z.); (Y.C.)
| | - Wei Liu
- School of Clinical Medicine, North China University of Science and Technology, Tangshan 063200, China; (W.L.); (Y.Z.); (W.K.); (X.S.); (L.H.)
| | - Yingze Zhu
- School of Clinical Medicine, North China University of Science and Technology, Tangshan 063200, China; (W.L.); (Y.Z.); (W.K.); (X.S.); (L.H.)
| | - Wenyue Kong
- School of Clinical Medicine, North China University of Science and Technology, Tangshan 063200, China; (W.L.); (Y.Z.); (W.K.); (X.S.); (L.H.)
| | - Xin Su
- School of Clinical Medicine, North China University of Science and Technology, Tangshan 063200, China; (W.L.); (Y.Z.); (W.K.); (X.S.); (L.H.)
| | - Lanxiang Huang
- School of Clinical Medicine, North China University of Science and Technology, Tangshan 063200, China; (W.L.); (Y.Z.); (W.K.); (X.S.); (L.H.)
| | - Yishuang Cui
- School of Public Health, North China University of Science and Technology, Tangshan 063200, China; (X.Z.); (Y.C.)
| | - Guogui Sun
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan 063000, China
- Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, China
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Huang D, Chu Y, Qiu J, Chen X, Zhao J, Zhang Y, Li S, Cheng Y, Shi H, Han L, Wang J. A novel diagnostic signature of circulating tsRNAs and miRNAs in esophageal squamous cell carcinoma detected with a microfluidic platform. Anal Chim Acta 2023; 1272:341520. [PMID: 37355337 DOI: 10.1016/j.aca.2023.341520] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 06/07/2023] [Accepted: 06/09/2023] [Indexed: 06/26/2023]
Abstract
Small non-coding RNAs (sncRNAs) consisting of tRNA-derived small RNAs (tsRNAs) and miRNAs can be released by cancer cells and detected in blood, offering great potential for diagnosis of malignant tumors such as squamous cell carcinoma of the esophagus (ESCC). One of the major challenges for the clinical application of blood-based sncRNAs biomarkers is the difficulty of detection because of their small sncRNA size and low abundance. The deferentially expressed tsRNAs and miRNAs in plasma were studied with high-throughput sequencing and polymerase chain reaction in ESCC cohorts. A novel signature containing tRF-55:74-chrM.Phe-GAA, tRF-56:75-Ala-CGC-1-M4 and miR-4488 was identified with diagnostic potential. The signature was further confirmed by an attomolar-level ultrasensitive and rapid microfluidic biochip, which can achieve a multiplex, simple and low-cost detection. Our results indicated that a combination of tsRNAs and miRNAs has high diagnostic efficiency and tremendous potential to act as specific biomarkers through a reliable, highly sensitive, fast, and economic microfluidic biochip for ESCC diagnosis.
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Affiliation(s)
- Di Huang
- Department of Radiation Oncology, Qilu Hospital of Shandong University, Shandong University, Jinan, 250012, China
| | - Yujin Chu
- Institute of Marine Science and Technology, Shandong University, Qingdao, 266237, China
| | - Jiaoyan Qiu
- Institute of Marine Science and Technology, Shandong University, Qingdao, 266237, China
| | - Xiaoshuang Chen
- Institute of Marine Science and Technology, Shandong University, Qingdao, 266237, China
| | - Junhua Zhao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, 110001, China; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors of Ministry of Education, China Medical University, Shenyang, 110001, China
| | - Yu Zhang
- Institute of Marine Science and Technology, Shandong University, Qingdao, 266237, China
| | - Shunjia Li
- Department of Radiation Oncology, Qilu Hospital of Shandong University, Shandong University, Jinan, 250012, China
| | - Yufeng Cheng
- Department of Radiation Oncology, Qilu Hospital of Shandong University, Shandong University, Jinan, 250012, China
| | - Han Shi
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, 110001, China; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors of Ministry of Education, China Medical University, Shenyang, 110001, China
| | - Lin Han
- Institute of Marine Science and Technology, Shandong University, Qingdao, 266237, China.
| | - Jianbo Wang
- Department of Radiation Oncology, Qilu Hospital of Shandong University, Shandong University, Jinan, 250012, China.
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Zhang WT, Wang YJ, Zhang GX, Zhang YH, Gao SS. Diagnostic value of circulating microRNAs for esophageal cancer: a meta-analysis based on Asian data. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:504-514. [PMID: 35040334 DOI: 10.17235/reed.2022.8348/2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND OBJECTIVE esophageal cancer (EC) is one of the most common gastrointestinal malignant diseases. We conducted a comprehensive meta-analysis to explore the clinical applicability of circulating microRNA for the diagnosis of EC. METHODS as of September 10, 2021, a comprehensive literature search was conducted on PubMed, Embase, Web of Science, Cochrane Library, Wanfang Database, and China National Knowledge Infrastructure (CNKI) to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled to evaluate the test performance. The potential sources of heterogeneity were analyzed by subgroup analysis. Deeks' funnel plot was used to assess publication bias. RESULTS 85 studies from 50 articles were included in the current meta-analysis. The overall pooled sensitivity was 0.82 (95 % CI, 0.79-0.84), specificity was 0.84 (95 % CI, 0.81-0.86), PLR was 4.9 (95 % CI, 4.2-5.9), NLR was 0.22 (95 % CI, 0.19-0.25), DOR was 22 (95 % CI, 17-29) and AUC was 0.89 (95 % CI, 0.86-0.92), respectively. Subgroup analysis suggested that miRNA clusters with a large sample size showed better diagnostic accuracy. Publication bias was not found. CONCLUSIONS circulating miRNAs can be used as a potential non-invasive biomarker for the diagnosis of EC in Asian populations.
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Yang H, Li X, Yang W. Advances in targeted therapy and immunotherapy for esophageal cancer. Chin Med J (Engl) 2023; 136:1910-1922. [PMID: 37403208 PMCID: PMC10431250 DOI: 10.1097/cm9.0000000000002768] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Indexed: 07/06/2023] Open
Abstract
ABSTRACT Esophageal cancer (EC) is one of the most common aggressive malignant tumors in the digestive system with a severe epidemiological situation and poor prognosis. The early diagnostic rate of EC is low, and most EC patients are diagnosed at an advanced stage. Multiple multimodality treatments have gradually evolved into the main treatment for advanced EC, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. And the emergence of targeted therapy and immunotherapy has greatly improved the survival of EC patients. This review highlights the latest advances in targeted therapy and immunotherapy for EC, discusses the efficacy and safety of relevant drugs, summarizes related important clinical trials, and tries to provide references for therapeutic strategy of EC.
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Affiliation(s)
- Haiou Yang
- Cancer center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi 030032, China
| | - Xuewei Li
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Wenhui Yang
- Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030001, China
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Cheng M, Xin Q, Ma S, Ge M, Wang F, Yan X, Jiang B. Advances in the Theranostics of Oesophageal Squamous Carcinoma. ADVANCED THERAPEUTICS 2023; 6. [DOI: 10.1002/adtp.202200251] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Indexed: 01/04/2025]
Abstract
AbstractOesophageal squamous carcinoma (ESCC) is one of the most lethal human malignancies, and it is a more aggressive form of oesophageal cancer (EC) that comprises over 90% of all EC cases in China compared with oesophageal adenocarcinoma (EAC). The high mortality of ESCC is attributed to the late‐stage diagnosis, chemoradiotherapy resistance, and lack of appropriate therapeutic targets and corresponding therapeutic formulations. Recently, emerging clinical and translational investigations have involved genome analyses, diagnostic biomarkers, and targeted therapy for ESCC, and these studies provide a new horizon for improving the clinical outcomes of patients with ESCC. Here, the latest research advances in the theranostics of ESCC are reviewed and the unique features of ESCC (including differences from EAC, genomic alterations, and microbe infections), tissue and circulating biomarkers, chemoradiotherapy resistance, clinical targeted therapy for ESCC, identification of novel therapeutic targets, and designation of nanotherapeutic systems for ESCC are particularly focused on. Finally, the perspectives for future clinical and translational theranostic research of ESCC are discussed and the obstacles that must be overcome in ESCC theranostics are described.
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Affiliation(s)
- Miaomiao Cheng
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Qi Xin
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Saiyu Ma
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Mengyue Ge
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Feng Wang
- Oncology Department The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450000 China
| | - Xiyun Yan
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
- State Key Laboratory of Esophageal Cancer Prevention &Treatment Zhengzhou Henan 450001 China
- CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide Pharmaceuticals Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China
| | - Bing Jiang
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
- State Key Laboratory of Esophageal Cancer Prevention &Treatment Zhengzhou Henan 450001 China
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Doghish AS, El-Husseiny AA, Abdelmaksoud NM, El-Mahdy HA, Elsakka EGE, Abdel Mageed SS, Mahmoud AMA, Raouf AA, Elballal MS, El-Dakroury WA, AbdelRazek MMM, Noshy M, El-Husseiny HM, Abulsoud AI. The interplay of signaling pathways and miRNAs in the pathogenesis and targeted therapy of esophageal cancer. Pathol Res Pract 2023; 246:154529. [PMID: 37196470 DOI: 10.1016/j.prp.2023.154529] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/19/2023]
Abstract
Globally, esophageal cancer (EC) is the 6th leading cause of cancer-related deaths and the second deadliest gastrointestinal cancer. Multiple genetic and epigenetic factors, such as microRNAs (miRNAs), influence its onset and progression. miRNAs are short nucleic acid molecules that can regulate multiple cellular processes by regulating gene expression. Therefore, EC initiation, progression, apoptosis evasions, invasion capacity, promotion, angiogenesis, and epithelial-mesenchymal transition (EMT) enhancement are associated with miRNA expression dysregulation. Wnt/-catenin signaling, Mammalian target of rapamycin (mTOR)/P-gp, phosphoinositide-3-kinase (PI3K)/AKT/c-Myc, epidermal growth factor receptor (EGFR), and transforming growth factor (TGF)-β signaling are crucial pathways in EC that are controlled by miRNAs. This review was conducted to provide an up-to-date assessment of the role of microRNAs in EC pathogenesis and their modulatory effects on responses to various EC treatment modalities.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Ahmed A El-Husseiny
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Cairo, Egypt
| | - Nourhan M Abdelmaksoud
- Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Abdulla M A Mahmoud
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed Amr Raouf
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohamed M M AbdelRazek
- Department of Pharmacognosy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mina Noshy
- Clinical Pharmacy Department, Faculty of Pharmacy, King Salman International University (KSIU), SouthSinai, Ras Sudr 46612, Egypt
| | - Hussein M El-Husseiny
- Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan; Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
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Ke S, Wang J, Lu J, Fang M, Li R. Long intergenic non-protein coding RNA 00858 participates in the occurrence and development of esophageal squamous cell carcinoma through the activation of the FTO-m6A-MYC axis by recruiting ZNF184. Genomics 2023; 115:110593. [PMID: 36868327 DOI: 10.1016/j.ygeno.2023.110593] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 02/10/2023] [Accepted: 02/26/2023] [Indexed: 03/05/2023]
Abstract
OBJECTIVES We aimed at probing impact of LINC00858 on esophageal squamous cell carcinoma (ESCC) progression via ZNF184-FTO-m6A-MYC axis. METHODS Expression of related genes (LINC00858, ZNF184, FTO, and MYC) was detected in ESCC tissues or cells and their relationships were assessed. After expression alterations in ESCC cells, cell proliferation, invasion, migration, and apoptosis were detected. Tumor formation in nude mice was conducted. RESULTS LINC00858, ZNF184, FTO, and MYC were overexpressed in ESCC tissues and cells. LINC00858 enhanced ZNF184 expression to upregulate FTO, which augmented MYC expression. LINC00858 knockdown diminished ESCC cell proliferative, migratory, and invasive properties while elevating apoptosis, which was negated by FTO overexpression. FTO knockdown exerted similar functions of LINC00858 knockdown on ESCC cell movements, which was annulled by MYC upregulation. Silencing LINC00858 repressed tumor growth and related gene expression in nude mice. CONCLUSIONS LINC00858 modulated MYC m6A modification via FTO by recruiting ZNF184, thus facilitating ESCC progression.
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Affiliation(s)
- Shun Ke
- Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China; Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China
| | - Jing Wang
- Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430071, PR China
| | - Jun Lu
- Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China; Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China
| | - Minghao Fang
- Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China; Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China
| | - Ruichao Li
- Department of General Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
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Pappen E, Morschbacher AP, Granada CE, Contini V, Henriques JAP. Evolution of the scientific literature on esophageal cancer from 1945 to 2020: a bibliometric analysis. AN ACAD BRAS CIENC 2023; 95:e20220716. [PMID: 36790272 DOI: 10.1590/0001-3765202320220716] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 10/12/2022] [Indexed: 02/12/2023] Open
Abstract
The aim of this study was to use bibliometric techniques to provide a longitudinal view of the evolution over more than 50 years of the literature on esophageal cancer without focusing on a specific area. The Web of Science Core Collection database was searched for published articles on esophageal neoplasm. Different aspects of the articles were analyzed - country, journal, authors, keywords, and topics. The search returned 24,215 articles - the journal Diseases of the Esophagus present the most number of manuscripts (n = 858), followed by Annals of Surgical Oncology (n = 475).The most cited article was one by van Hagen et al. (2012) (2,807 citations). The most prevalent topic was oncology (n = 10,448), followed by surgery (n = 4,944). Most articles were original research (n = 22,697), mainly with the basic science study design and published by institutions in China. The analysis of the variables chosen, identified China as the country with the highest number of articles and showed that authors and institutions in Asia stand out when it comes to production of scientific information on esophageal cancer.
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Affiliation(s)
- Emelin Pappen
- Universidade do Vale do Taquari (Univates), Graduate Program in Biotechnology, Avelino Talini Avenue, 171, 95914-014 Lajeado, RS, Brazil
| | - Ana Paula Morschbacher
- Universidade do Vale do Taquari (Univates), Graduate Program in Biotechnology, Avelino Talini Avenue, 171, 95914-014 Lajeado, RS, Brazil
| | - Camille E Granada
- Universidade do Vale do Taquari (Univates), Graduate Program in Biotechnology, Avelino Talini Avenue, 171, 95914-014 Lajeado, RS, Brazil
| | - Verônica Contini
- Universidade do Vale do Taquari (Univates), Graduate Program in Biotechnology, Avelino Talini Avenue, 171, 95914-014 Lajeado, RS, Brazil.,Universidade do Vale do Taquari (Univates), Graduate Program in Medical Science, Avelino Talini Avenue, 171, 95914-014 Lajeado, RS, Brazil
| | - João Antonio P Henriques
- Universidade do Vale do Taquari (Univates), Graduate Program in Biotechnology, Avelino Talini Avenue, 171, 95914-014 Lajeado, RS, Brazil.,Universidade do Vale do Taquari (Univates), Graduate Program in Medical Science, Avelino Talini Avenue, 171, 95914-014 Lajeado, RS, Brazil
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Biomarkers for Early Detection, Prognosis, and Therapeutics of Esophageal Cancers. Int J Mol Sci 2023; 24:ijms24043316. [PMID: 36834728 PMCID: PMC9968115 DOI: 10.3390/ijms24043316] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 01/31/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
Esophageal cancer (EC) is the deadliest cancer worldwide, with a 92% annual mortality rate per incidence. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of ECs, with EAC having one of the worst prognoses in oncology. Limited screening techniques and a lack of molecular analysis of diseased tissues have led to late-stage presentation and very low survival durations. The five-year survival rate of EC is less than 20%. Thus, early diagnosis of EC may prolong survival and improve clinical outcomes. Cellular and molecular biomarkers are used for diagnosis. At present, esophageal biopsy during upper endoscopy and histopathological analysis is the standard screening modality for both ESCC and EAC. However, this is an invasive method that fails to yield a molecular profile of the diseased compartment. To decrease the invasiveness of the procedures for diagnosis, researchers are proposing non-invasive biomarkers for early diagnosis and point-of-care screening options. Liquid biopsy involves the collection of body fluids (blood, urine, and saliva) non-invasively or with minimal invasiveness. In this review, we have critically discussed various biomarkers and specimen retrieval techniques for ESCC and EAC.
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Sheikh M, Roshandel G, McCormack V, Malekzadeh R. Current Status and Future Prospects for Esophageal Cancer. Cancers (Basel) 2023; 15:765. [PMID: 36765722 PMCID: PMC9913274 DOI: 10.3390/cancers15030765] [Citation(s) in RCA: 102] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 01/10/2023] [Accepted: 01/20/2023] [Indexed: 01/28/2023] Open
Abstract
Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence of ESCC is declining, the incidence of EAC is increasing in many countries. Decades of epidemiologic research have identified distinct environmental exposures for ESCC and EAC subtypes. Recent advances in understanding the genomic aspects of EC have advanced our understanding of EC causes and led to using specific genomic alterations in EC tumors as biomarkers for early diagnosis, treatment, and prognosis of this cancer. Nevertheless, the prognosis of EC is still poor, with a five-year survival rate of less than 20%. Currently, there are significant challenges for early detection and secondary prevention for both ESCC and EAC subtypes, but Cytosponge™ is shifting this position for EAC. Primary prevention remains the preferred strategy for reducing the global burden of EC. In this review, we will summarize recent advances, current status, and future prospects of the studies related to epidemiology, time trends, environmental risk factors, prevention, early diagnosis, and treatment for both EC subtypes.
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Affiliation(s)
- Mahdi Sheikh
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Gholamreza Roshandel
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 49341-74515, Iran
| | - Valerie McCormack
- Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 14117-13135, Iran
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Yu Q, Xia N, Zhao Y, Jin H, Chen R, Ye F, Chen L, Xie Y, Wan K, Zhou J, Zhou D, Lv X. Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection. BMC Med Genomics 2022; 15:247. [PMID: 36447287 PMCID: PMC9706897 DOI: 10.1186/s12920-022-01401-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 11/22/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease. METHODS The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC. RESULTS We obtained 438,558 DMCs, 15,462 DMRs, and 1568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC. The HOXL-score estimated by HOXC10 and HOXD1 methylation, whose methylation status were then confirmed by sanger sequencing in our custom ESCC samples, showed good ability in discriminating ESCC from normal samples. CONCLUSIONS We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of esophageal squamous cell carcinoma.
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Affiliation(s)
- Qiuning Yu
- grid.412633.10000 0004 1799 0733Otorhinolaryngology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Namei Xia
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Yanteng Zhao
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Huifang Jin
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Renyin Chen
- grid.412633.10000 0004 1799 0733Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Fanglei Ye
- grid.412633.10000 0004 1799 0733Otorhinolaryngology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Liyinghui Chen
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Ying Xie
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Kangkang Wan
- Wuhan Ammunition Life-tech Company, Ltd., Wuhan, Hubei China
| | - Jun Zhou
- Wuhan Ammunition Life-tech Company, Ltd., Wuhan, Hubei China
| | - Dihan Zhou
- Wuhan Ammunition Life-tech Company, Ltd., Wuhan, Hubei China
| | - Xianping Lv
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
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Kong Z, Sun F, Meng Q, Zhou M, Yu J, Hu L. Investigating the predictive value of vascular endothelial growth factor in the evaluation of treatment efficacy and prognosis for patients with non-surgical esophageal squamous cell carcinoma. Front Oncol 2022; 12:843250. [PMID: 36387083 PMCID: PMC9644112 DOI: 10.3389/fonc.2022.843250] [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: 12/25/2021] [Accepted: 09/20/2022] [Indexed: 11/29/2022] Open
Abstract
In this study, we aim to investigate the predictive value of serum vascular endothelial growth factor (VEGF) in evaluating treatment efficacy and long-term prognosis for patients with non-surgical esophageal squamous cell carcinoma (ESCC). The patients diagnosed with ESCC by histopathology who didn’t receive surgical treatment were retrospectively analyzed. Through follow-up and prognostic analysis, we explored the value of serum VEGF changes before, during, and after radiotherapy for predicting treatment efficacy, and identified important indicators to construct the predictive model. Eighty-four patients were enrolled in this study, and the objective response rate (ORR) after treatment was 75.0%. The serum VEGF before, during and after radiotherapy were 108.2 ± 38.4, 98.6 ± 20.3 and 96.9 ± 20.0pg/ml, respectively. Staging and serum VEGF during radiotherapy were the independent factors affecting the treatment efficacy of non-surgical ESCC patients (OR=0.182 and 0.959, P<0.05). The median overall survival (OS) and progression-free survival (PFS) were 24.4 and 15.8 months. The 3-year, 5-year, 10-year OS rates and PFS rates were 35.7%, 26.2%, 14.4%, and 26.2%, 22.6%, 12.3%, respectively. By performing COX regression analysis, we found that the TNM stage, changes of VEGF after radiotherapy (∆VEGF2), and endoscopic histopathological response were the independent prognostic factors for OS and PFS (P<0.05). The R2 of the constructed prediction model was 0.328 and 0.362, and the C-index was 0.697 and 0.708, respectively. The follow-up time-dependent AUC showed that the predicted AUC was stable and greater than 0.7 as the follow-up time increased. For patients with non-surgical ESCC, those with low VEGF levels during radiotherapy had better treatment efficacy, and those with significant VEGF reduction after radiotherapy had a better prognosis. In summary, our results demonstrate that it is feasible to construct a model to evaluate and predict the efficacy and prognosis of patients with non-surgical ESCC based on serum VEGF measurement.
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Affiliation(s)
- Ze Kong
- Department of Radiation Oncology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
| | - Fei Sun
- Department of Radiation Oncology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
| | - Qinghong Meng
- Department of Radiation Oncology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
| | - Mengyun Zhou
- Department of Radiation Oncology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
| | - Jingping Yu
- Department of Radiation Oncology, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
- *Correspondence: Lijun Hu, ; Jingping Yu,
| | - Lijun Hu
- Department of Radiation Oncology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
- *Correspondence: Lijun Hu, ; Jingping Yu,
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Machine Learning and Novel Biomarkers Associated with Immune Infiltration for the Diagnosis of Esophageal Squamous Cell Carcinoma. JOURNAL OF ONCOLOGY 2022; 2022:6732780. [PMID: 36081670 PMCID: PMC9448540 DOI: 10.1155/2022/6732780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 07/08/2022] [Accepted: 07/13/2022] [Indexed: 11/18/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) accounts for the main esophageal cancer type, which is related to advanced stage and poor survivals. Therefore, novel diagnostic biomarkers are critically needed. In the current research, we aimed to screen novel diagnostic biomarkers based on machine learning. The expression profiles were obtained from GEO datasets (GSE20347, GSE38129, and GSE75241) and TCGA datasets. Differentially expressed genes (DEGs) were screened between 47 ESCC and 47 nontumor samples. The LASSO regression model and SVM-RFE analysis were carried out for the identification of potential markers. ROC analysis was carried out to assess discriminatory abilities. The expressions and diagnostic values of the candidates in ESCC were demonstrated in the GSE75241 datasets and TCGA datasets. We also explore the correlations between the critical genes and cancer immune infiltrates using CIBERSORT. In this study, we identified 27 DEGs in ESCC: 5 genes were significantly elevated, and 22 genes were significantly decreased. Based on the results of the SVM-RFE and LASSO regression model, we identified five potential diagnostic biomarkers for ESCC, including GPX3, COL11A1, EREG, MMP1, and MMP12. However, the diagnostic values of only GPX3, MMP1, and MMP12 were confirmed in GSE75241 datasets. Moreover, in TCGA datasets, we further confirmed that GPX3 expression was distinctly decreased in ESCC specimens, while the expression of MMP1 and MMP12 was noticeably increased in ESCC specimens. Immune cell infiltration analysis revealed that the expression of GPX3, MMP1, and MMP12 was associated with several immune, such as T cells CD8, macrophages M2, macrophages M0, and dendritic cells activated. Overall, our findings suggested GPX3, MMP1, and MMP12 as novel diagnostic marker and correlated with immune infiltrates in ESCC patients.
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Wong MCS, Deng Y, Huang J, Bai Y, Wang HHX, Yuan J, Zhang L, Yip HC, Chiu PWY. Performance of screening tests for esophageal squamous cell carcinoma: a systematic review and meta-analysis. Gastrointest Endosc 2022; 96:197-207.e34. [PMID: 35413332 DOI: 10.1016/j.gie.2022.04.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 04/04/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS This systematic review and meta-analysis aims to compare the pooled diagnostic accuracy of the currently available esophageal squamous cell carcinoma (ESCC) screening tests. METHODS A comprehensive literature search of Embase and Medline (up to October 31, 2020) was performed to identify eligible studies. We pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for ESCC screening tools using a bivariate random-effects model. The summary receiver operating characteristic curves with area under the curve (AUC) were plotted for each screening test. RESULTS We included 161 studies conducted in 81 research articles involving 32,209 subjects. The pooled sensitivity, specificity, and AUC of the major screening tools were respectively as follows: endoscopy (peroral endoscopy): .94 (95% confidence interval [CI], .87-.97), .92 (95% CI, .87-.95), and .97 (95% CI, .96-.99); endoscopy (transnasal endoscopy): .85 (95% CI, .70-.93), .96 (95% CI, .91-.98), and .97 (95% CI, .95-.98); microRNA: .77 (95% CI, .75-.80), .78 (95% CI, .75-.80), and .85 (95% CI, .81-.87); autoantibody: .45 (95% CI, .36-.53), .91 (95% CI, .89-.93), and .84 (95% CI, .81-.87); and cytology: .82 (95% CI, .60-.93), .97 (95% CI, .88-.99), and .97 (95% CI, .95-.98). There was high heterogeneity. CONCLUSIONS The diagnostic accuracy seemed to be comparable between cytology and endoscopy, whereas autoantibody and microRNAs bear potential as future noninvasive screening tools for ESCC. To reduce ESCC-related death in high-risk populations, it is important to develop a more accurate and less-invasive screening test.
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Affiliation(s)
- Martin C S Wong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China; School of Public Health, Peking Union Medical College and The Chinese Academy of Medical Sciences, Beijing, China; Department of Global Health, School of Public Health, Peking University, Beijing, China
| | - Yunyang Deng
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Junjie Huang
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yijun Bai
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Harry H X Wang
- School of Public Health, Sun Yat-Sen University, Guangzhou, China; General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, Scotland, UK
| | - Jinqiu Yuan
- Clinical Research Centre, Scientific Research Centre, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Lin Zhang
- School of Public Health, Peking Union Medical College and The Chinese Academy of Medical Sciences, Beijing, China; Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Hon Chi Yip
- Department of Surgery, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Philip Wai Yan Chiu
- Department of Surgery, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
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Song D, Wei Y, Hu Y, Sun Y, Liu M, Ren Q, Hu Z, Guo Q, Wang Y, Zhou Y. Identification of immunophenotypes in esophageal squamous cell carcinoma based on immune gene sets. Clin Transl Oncol 2022; 24:1100-1114. [PMID: 35098447 DOI: 10.1007/s12094-021-02749-9] [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: 10/13/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023]
Abstract
PURPOSE Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high heterogeneity. Research on molecular mechanisms involved in the process of tumor origination and progression is extremely limited to investigating mechanisms of molecular typing for ESCC. METHODS After comprehensively analyzing the gene expression profiles in The Cancer Genome Atlas and Gene Expression Omnibus databases, we identified four immunotypes of ESCC (referred to as C1-C4) based on the gene sets of 28 immune cell subpopulations. The discrepancies in prognostic value, clinical features, drug sensitivity, and tumor components between the immunotypes were individually analyzed. RESULTS The ranking of immune infiltration is C1 > C4 > C3 > C2. These subtypes are characterized by high and low expression of immune checkpoint proteins, enrichment and insufficiency of immune-related pathways, and differential distribution of immune cell subgroups. Poorer survival was observed in the C1 subtype, which we hypothesized could be caused by an immunosuppressive cell population. Fortunately, C1's susceptibility to anti-PD-1 therapy offers hope for patients with poor prognosis in advanced stages. On the other hand, C4 is sensitive to docetaxel, which may offer novel treatment strategies for ESCC in the future. It is worth noting that immunophenotyping is tightly bound to the abundance of stromal components and stem cells, which could explain the tumor immune escape to some extent. Ultimately, determination of hub genes based on the C1 subtypes provides a reference for the discovery of immunotarget drugs against ESCC. CONCLUSION The identification of immunophenotypes in our study provides new therapeutic strategies for patients with ESCC.
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Affiliation(s)
- Danlei Song
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China
| | - Yongjian Wei
- The First Department of Hepatobiliary and Pancreatic Surgery, Cangzhou Central Hospital, Cangzhou, China
| | - Yuping Hu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Hospital of Reproductive Medicine, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yueting Sun
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China
| | - Min Liu
- Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China
| | - Qian Ren
- Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China
| | - Zenan Hu
- Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China
| | - Qinghong Guo
- Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China
| | - Yuping Wang
- Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China
| | - Yongning Zhou
- The First Clinical Medical College, Lanzhou University, Lanzhou, China.
- Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China.
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Scherübl H. Tobacco Smoking and Gastrointestinal Cancer Risk. Visc Med 2022; 38:217-222. [PMID: 35814979 PMCID: PMC9209969 DOI: 10.1159/000523668] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 02/14/2022] [Indexed: 08/14/2023] Open
Abstract
Background Smoking tobacco is the most preventable cause of gastrointestinal (GI) cancer disease in Germany. The more and the longer you smoke, the higher your risk of GI cancer. About 28% of 18-64 year-old Germans are current smokers; in addition, 11% of the population is regularly exposed to secondhand tobacco smoke. Summary Tobacco use is causally associated with esophageal, gastric, pancreatic, biliary, hepatocellular, colorectal, and anal cancers. Combining smoking with alcohol use, excess body weight, diabetes, or chronic infections synergistically enhances GI cancer risk. Smoking cessation effectively reduces tobacco-associated GI cancer risk. Key Messages Smokers should be encouraged to stop smoking tobacco and join programs of risk-adaptive cancer screening.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin II, Gastroenterologie, GI Onkologie, Diabetologie und Infektiologie, Klinikum Am Urban, Vivantes Netzwerk für Gesundheit, Berlin, Germany
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Zhu Y, Li F, Wan Y, Liang H, Li S, Peng B, Shao L, Xu Y, Jiang D. Cancer-Secreted Exosomal MiR-620 Inhibits ESCC Aerobic Glycolysis via FOXM1/HER2 Pathway and Promotes Metastasis. Front Oncol 2022; 12:756109. [PMID: 35651785 PMCID: PMC9148961 DOI: 10.3389/fonc.2022.756109] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 01/17/2022] [Indexed: 11/30/2022] Open
Abstract
Background Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide. MicroRNAs (MiRNAs) have been reported to regulate cell functions through exosomes. Through the Gene Expression Omnibus (GEO) database, miR-620 was selected as a serum miRNA highly expressed in ESCC, but its detailed role in ESCC has not been explored. Tumor-secreted miRNAs have been reported to promote cancer metastasis through reprogramming the aerobic glycolysis of lung fibroblasts. Therefore, we intended to verify whether exosomal miR-620 secreted in ESCC cells may regulate the aerobic glycolysis of lung fibroblasts. Methods The effect of miR-620 on the aerobic glycolysis of ESCC cells was firstly verified through bioinformatics prediction and mechanism assays. Exosomes secreted from ESCC cells was detected, and the influence of exosomal miR-620 in regulating the aerobic glycolysis of lung fibroblasts was then verified both in vitro and in vivo. Results MiR-620 inhibited ESCC malignancy and suppressed the aerobic glycolysis of ESCC cells via targeting Forkhead box M1 (FOXM1) and human epidermal growth factor receptor 2 (HER2). Moreover, exosomal miR-620 was highly secreted in ESCC and could regulate HFL1 aerobic glycolysis via FOXM1/HER2 signaling. Furthermore, exosomal miR-620 could promote ESCC metastasis by reprogramming the aerobic glycolysis of lung fibroblasts (HFL1). Conclusion Exosomal miR-620 secreted by ESCC cells inhibited the aerobic glycolysis via FOXM1/HER2 axis and promoted cancer metastasis.
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Affiliation(s)
- Yanbo Zhu
- Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou, China
| | - Fang Li
- Department of Human Anatomy and Histology & Embryology, The School of Biology & Basic Medical Sciences, Soochow University, Suzhou, China
| | - Yilong Wan
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Hansi Liang
- Jiangsu Institute of Clinical Immunology, Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Si Li
- Clinical Medicine Major, Soochow University Medical College, Suzhou, China
| | - Bo Peng
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Liqun Shao
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yunyun Xu
- Childrens’ Hospital Affiliated to Soochow University, Institute of Pediatrics, Suzhou, China
- *Correspondence: Dong Jiang, ; Yunyun Xu,
| | - Dong Jiang
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- *Correspondence: Dong Jiang, ; Yunyun Xu,
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Liu T, Wang X, Guo W, Shao F, Li Z, Zhou Y, Zhao Z, Xue L, Feng X, Li Y, Tan F, Zhang K, Xue Q, Gao S, Gao Y, He J. RNA Sequencing of Tumor-Educated Platelets Reveals a Three-Gene Diagnostic Signature in Esophageal Squamous Cell Carcinoma. Front Oncol 2022; 12:824354. [PMID: 35615147 PMCID: PMC9124963 DOI: 10.3389/fonc.2022.824354] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 03/29/2022] [Indexed: 12/24/2022] Open
Abstract
There is no cost-effective, accurate, and non-invasive method for the detection of esophageal squamous cell carcinoma (ESCC) in clinical practice. We aimed to investigate the diagnostic potential of tumor-educated platelets in ESCC. In this study, seventy-one ESCC patients and eighty healthy individuals were enrolled and divided into a training cohort (23 patients and 27 healthy individuals) and a validation cohort (48 patients and 53 healthy individuals). Next-generation RNA sequencing was performed on platelets isolated from peripheral blood of all participants, and a support vector machine/leave-one-out cross validation (SVM/LOOCV) approach was used for binary classification. A diagnostic signature composed of ARID1A, GTF2H2, and PRKRIR discriminated ESCC patients from healthy individuals with 91.3% sensitivity and 85.2% specificity in the training cohort and 87.5% sensitivity and 81.1% specificity in the validation cohort. The AUC was 0.924 (95% CI, 0.845–0.956) and 0.893 (95% CI, 0.821–0.966), respectively, in the training cohort and validation cohort. This 3-gene platelet RNA signature could effectively discriminate ESCC from healthy control. Our data highlighted the potential of tumor-educated platelets for the noninvasive diagnosis of ESCC. Moreover, we found that keratin and collagen protein families and ECM-related pathways might be involved in tumor progression and metastasis of ESCC, which might provide insights to understand ESCC pathobiology and advance novel therapeutics.
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Affiliation(s)
- Tiejun Liu
- 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
| | - Xin Wang
- 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
| | - Wei Guo
- 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
| | - Fei Shao
- 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
- Cancer Institute of the Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao, China
| | - Zitong Li
- 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
| | - Yang Zhou
- 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
| | - Zhihong Zhao
- 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
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoli Feng
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yin Li
- 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
| | - Fengwei Tan
- 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
| | - Kai Zhang
- Department of Medical Examination for Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qi Xue
- 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
- 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
| | - Shugeng Gao
- 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
- 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
| | - Yibo Gao
- 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
- 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
- *Correspondence: Yibo Gao, ; Jie He,
| | - Jie He
- 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
- 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
- *Correspondence: Yibo Gao, ; Jie He,
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Iacob R, Mandea M, Iacob S, Pietrosanu C, Paul D, Hainarosie R, Gheorghe C. Liquid Biopsy in Squamous Cell Carcinoma of the Esophagus and of the Head and Neck. Front Med (Lausanne) 2022; 9:827297. [PMID: 35572996 PMCID: PMC9098838 DOI: 10.3389/fmed.2022.827297] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/15/2022] [Indexed: 11/13/2022] Open
Abstract
Squamous cell carcinomas of the esophagus (ESCC) and of the head and neck (HNSCC) are two neoplasms that share common risk factors and have the same embryological origin, but a very different prognosis, the 5-year survival of HNSCC being almost double (40–50%) compared to the 5-year survival of ESCC (20%). Current guidelines emphasize the importance of screening for ESCC in patients diagnosed with head and neck cancers. A liquid biopsy is a novel tool for diagnosis, prognostic stratification, and personalized therapy. Liquid biopsy biomarkers for these two malignancies could help both their early detection, facilitate residual disease identification, and provide prognosis information. The present systematic review of the literature was aimed at describing the liquid biopsy biomarkers present in these two malignancies, with an emphasis on potential clinical applications.
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Affiliation(s)
- Razvan Iacob
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Matei Mandea
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
| | - Speranta Iacob
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Catalina Pietrosanu
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Professor Doctor Dorin Hociota Institute of Phonoaudiology and Functional ENT Surgery, Bucharest, Romania
| | - Doru Paul
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, United States
| | - Razvan Hainarosie
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Professor Doctor Dorin Hociota Institute of Phonoaudiology and Functional ENT Surgery, Bucharest, Romania
- *Correspondence: Razvan Hainarosie
| | - Cristian Gheorghe
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
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