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Cui W, Wang Y, Guo J, Zhang Z. Construction of a cuproptosis-associated long non-coding RNA risk prediction model for pancreatic adenocarcinoma based on the TCGA database. Medicine (Baltimore) 2023; 102:e32808. [PMID: 36749249 PMCID: PMC9901963 DOI: 10.1097/md.0000000000032808] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Cuproptosis is a recently identified controlled process of cell death that functions in tumor development and treatment. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that bind to transcription factors and regulate tumor invasion, penetration, metastasis, and prognosis. However, there are limited data on the function of cuproptosis-associated lncRNAs in pancreatic adenocarcinoma. Utilizing data retrieved from the cancer genome atlas database, we devised a risk prediction model of cuproptosis-associated lncRNAs in pancreatic adenocarcinoma, determined their prognostic significance and relationship with tumor immunity, and screened potential therapeutic drugs. Overall, 178 patients were randomized to a training or test group. We then obtained 6 characteristic cuproptosis-associated lncRNAs from the training group, based on which we constructed the risk prediction model, calculated the risk score, and verified the test group results. Subsequently, we performed differential gene analysis, tumor immunoassays, functional enrichment analysis, and potential drug screening. Finally, we found that the prediction model was highly reliable for the prognostic assessment of pancreatic adenocarcinoma patients. Generally, low risk patients had better outcomes than high risk patients. A tumor immunoassay showed that immunotherapy may benefit high risk patients more as there is a greater likelihood that the tumors could escape the immune system in low-risk patients. Through drug screening, we identified ten drugs that may have therapeutic effects on patients with pancreatic adenocarcinoma. In conclusion, this study constructed a risk prediction model of cuproptosis-associated lncRNAs, which can reliably predict the prognosis of pancreatic adenocarcinoma patients, provided a clinical reference for determining treatment approach, and provided some insights into the associations between lncRNAs and cuproptosis. This provides useful insight to aid in the development of therapeutic drugs for pancreatic adenocarcinoma.
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Affiliation(s)
- Wenguang Cui
- Hebei North University, Zhangjiakou, Hebei Province, China
- * Correspondence: Wenguang Cui, Hebei North University, No.11, South Diamond Road, Zhangjiakou, Hebei Province 075000, China (e-mail: )
| | - Yaling Wang
- The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, China
| | - Jianhong Guo
- Hebei North University, Zhangjiakou, Hebei Province, China
| | - Zepeng Zhang
- Hebei North University, Zhangjiakou, Hebei Province, China
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Zhong J, Liao X, Peng S, Cao J, Liu Y, Liu C, Qiu J, Guan X, Zhang Y, Liu X, Peng S. A Visualized Dynamic Prediction Model for Overall Survival in Elderly Patients With Pancreatic Cancer for Smart Medical Services. Front Public Health 2022; 10:885624. [PMID: 35685764 PMCID: PMC9171143 DOI: 10.3389/fpubh.2022.885624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/06/2022] [Indexed: 11/13/2022] Open
Abstract
Background Pancreatic cancer (PC) is a highly malignant tumor of the digestive system. The number of elderly patients with PC is increasing, and older age is related to a worse prognosis. Accurate prognostication is crucial in treatment decisions made for people diagnosed with PC. However, an accurate predictive model for the prognosis of these patients is still lacking. We aimed to construct nomograms for predicting the overall survival (OS) of elderly patients with PC. Methods Patients with PC, older than 65 years old from 2010 to 2015 in the Surveillance, Epidemiology, and End Results database, were selected and randomly divided into training cohort (n = 4,586) and validation cohort (n = 1,966). Data of patients in 2016-2018 (n = 1,761) were used for external validation. Univariable and forward stepwise multivariable Cox analysis was used to determine the independent prognostic factors. We used significant variables in the training set to construct nomograms predicting prognosis. The performance of the models was evaluated for their discrimination and calibration power based on the concordance index (C-index), calibration curve, and the decision curve analysis (DCA). Results Age, insurance, grade, surgery, radiation, chemotherapy, T, N, and American Joint Commission on Cancer were independent predictors for OS and thus were included in our nomogram. In the training cohort and validation cohort, the C-indices of our nomogram were 0.725 (95%CI: 0.715-0.735) and 0.711 (95%CI: 0.695-0.727), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves showed similar results. The calibration curves showed a high consensus between observations and predictions. In the external validation cohort, C-index (0.797, 95%CI: 0.778-0.816) and calibration curves also revealed high consistency between observations and predictions. The nomogram-related DCA curves showed better clinical utility compared to tumor-node-metastasis staging. In addition, we have developed an online prediction tool for OS. Conclusions A web-based prediction model for OS in elderly patients with PC was constructed and validated, which may be useful for prognostic assessment, treatment strategy selection, and follow-up management of these patients.
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Affiliation(s)
- Jiang Zhong
- College of Computer Science, Chongqing University, Chongqing, China
| | - XingShu Liao
- College of Computer Science, Chongqing University, Chongqing, China
| | - Shuang Peng
- General Affairs Section, The People's Hospital of Tongnan District, Chongqing, China
| | - Junyi Cao
- Department of Medical Quality Control, First People's Hospital of Zigong City, Zigong, China
| | - Yue Liu
- Department of Pediatrics, First People's Hospital of Zigong City, Zigong, China
| | - Chunyang Liu
- Scientific Research Department, First People's Hospital of Zigong City, Zigong, China
| | - Ju Qiu
- Scientific Research Department, First People's Hospital of Zigong City, Zigong, China
| | - Xiaoyan Guan
- Department of Pediatrics, First People's Hospital of Zigong City, Zigong, China
| | - Yang Zhang
- College of Medical Information, Chongqing Medical University, Chongqing, China
| | - Xiaozhu Liu
- Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shengxian Peng
- Scientific Research Department, First People's Hospital of Zigong City, Zigong, China
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Wang H, Cui J, Yu J, Huang J, Li M. Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma. Front Genet 2022; 13:855940. [PMID: 35464865 PMCID: PMC9023759 DOI: 10.3389/fgene.2022.855940] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 03/21/2022] [Indexed: 12/18/2022] Open
Abstract
Lung adenocarcinoma (LUAD) is one of the most common malignant tumors with poor prognosis. Fatty acid metabolism is associated with cancer progression and a poor prognosis. We searched for long noncoding RNAs (lncRNAs) associated with fatty acid metabolism to predict the overall survival (OS) of patients with LUAD. We obtained lncRNA expression profiles and clinical follow-up data related to fatty acid metabolism in patients with LUAD from The Cancer Genome Atlas and Molecular Signatures database. Patients were randomly divided into training, experimental, and combination groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression models were used to construct fatty acid metabolism-related prognostic markers, Kaplan-Meier analysis was used to compare the prognosis of each group, and receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of the prognostic model. We used the pRRophetic algorithm to assess the treatment response based on the half-maximal inhibitory concentration (IC50) of each sample in the Genomics of Cancer Drug Sensitivity (GDSC) database. A fatty acid metabolism-related prognostic marker containing seven lncRNAs was constructed to predict OS in LUAD. In the training, test and combination groups, the patients were divided into high- and low-risk groups according to a formula. K–M analysis showed that patients in the high-risk group had poorer prognosis, with significant differences in the subgroup analysis. ROC analysis showed that the predictive ability of the model was more accurate. A clinical prediction nomogram combining lncRNA and clinical features was constructed to accurately predict OS and had high clinical application value. Therapeutics were screened based on the IC50 values of each sample in the GDSC database. We found that A.443654, AUY922, AZ628, A.770041, AZD.0530, AMG.706, and AG.014699 were more effective in high-risk patients. We constructed a 7-lncRNA prognostic model to predict the OS of patients with LUAD. In addition, the predictive nomogram model based on our established seven fatty acid metabolism-related lncRNA signatures provides better clinical value than that of the traditional TNM staging system in predicting the prognosis of patients with LUAD and presents new insights for personalized treatment.
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Affiliation(s)
- Helin Wang
- Departments of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Henan, China
| | - Junwei Cui
- Departments of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, Henan, China
| | - Jian Yu
- Departments of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Henan, China
| | - Jian Huang
- Departments of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, Henan, China
| | - Mingying Li
- Departments of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, Henan, China
- *Correspondence: Mingying Li,
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Yang M, Liu Q, Dai M, Peng R, Li X, Zuo W, Gou J, Zhou F, Yu S, Liu H, Huang M. FOXQ1-mediated SIRT1 upregulation enhances stemness and radio-resistance of colorectal cancer cells and restores intestinal microbiota function by promoting β-catenin nuclear translocation. J Exp Clin Cancer Res 2022; 41:70. [PMID: 35183223 PMCID: PMC8857837 DOI: 10.1186/s13046-021-02239-4] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 12/28/2021] [Indexed: 01/01/2023] Open
Abstract
Background Resistance of colorectal cancer (CRC) cells to radiotherapy considerably contributes to poor clinical outcomes of CRC patients. Microarray profiling in this study revealed the differentially expressed forkhead box Q1 (FOXQ1) in CRC, and thus we aimed to illustrate the role of FOXQ1 in CRC by modulating stemness and radio-resistance of CRC cells. Methods CRC and adjacent normal tissues were collected from CRC patients, and the correlation between FOXQ1 expression and CRC prognosis was analyzed. Subsequently, we determined the expression of FOXQ1, sirtuin 1 (SIRT1) and β-catenin in CRC tissues and cell lines. The binding affinity between FOXQ1 and SIRT1 and that between SIRT1 and β-catenin were validated with luciferase reporter gene, Co-IP and ChIP assays. Following a metagenomics analysis of CRC intestinal microbiota, the effects of the FOXQ1/SIRT1/β-catenin axis on CRC stem cell phenotypes and radio-resistance was evaluated in vitro and in vivo through manipulation of gene expression. Besides, mouse feces were collected to examine changes in intestinal microbiota. Results FOXQ1 was highly expressed in CRC tissues and cells and positively correlated with poor prognosis of CRC patients. FOXQ1 overexpression contributed to resistance of CRC cells to radiation. Knockdown of FOXQ1 inhibited the stemness of CRC cells and reversed their radio-resistance. FOXQ1 enhanced the transcriptional expression of SIRT1, and SIRT1 enhanced the expression and nuclear translocation of β-catenin. Knockdown of FOXQ1 repressed SIRT1 expression, thus reducing the stemness and radio-resistance of CRC cells. Moreover, FOXQ1 knockdown suppressed CRC xenograft formation in xenograft-bearing nude mice through inhibiting SIRT1 and β-catenin to reduce the content of pathological bacteria that were up-regulated in CRC. Conclusion FOXQ1-mediated SIRT1 upregulation augments expression and nuclear translocation of β-catenin and benefits CRC-related intestinal pathological bacterial, thereby enhancing the stemness and radio-resistance of CRC cells. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-02239-4.
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Bai S, Chen L, Yan Y, Wang X, Jiang A, Li R, Kang H, Feng Z, Li G, Ma W, Zhang J, Ren J. Identification of Hypoxia-Immune-Related Gene Signatures and Construction of a Prognostic Model in Kidney Renal Clear Cell Carcinoma. Front Cell Dev Biol 2022; 9:796156. [PMID: 35211477 PMCID: PMC8860910 DOI: 10.3389/fcell.2021.796156] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 12/23/2021] [Indexed: 12/24/2022] Open
Abstract
Introduction: Kidney renal clear cell carcinoma (KIRC), a kind of malignant disease, is a severe threat to public health. Tracking the information of tumor progression and conducting a related dynamic prognosis model are necessary for KIRC. It is crucial to identify hypoxia-immune-related genes and construct a prognostic model due to immune interaction and the influence of hypoxia in the prognosis of patients with KIRC. Methods: The hypoxia and immune status of KIRC patients were identified by utilizing t-SNE and ImmuCellAI for gene expression data. COX and Lasso regression were used to identify some hypoxia-immune-related signature genes and further construct a prognostic risk model based on these genes. Internal and external validations were also conducted to construct a prognostic model. Finally, some potentially effective drugs were screened by the CMap dataset. Results: We found that high-hypoxia and low-immune status tend to induce poor overall survival (OS). Six genes, including PLAUR, UCN, PABPC1L, SLC16A12, NFE2L3, and KCNAB1, were identified and involved in our hypoxia-immune-related prognostic risk model. Internal verification showed that the area under the curve (AUC) for the constructed models for 1-, 3-, 4-, and 5-year OS were 0.768, 0.754, 0.775, and 0.792, respectively. For the external verification, the AUC for 1-, 3-, 4-, and 5-year OS were 0.768, 0.739, 0.763, and 0.643 respectively. Furthermore, the decision curve analysis findings demonstrated excellent clinical effectiveness. Finally, we found that four drugs (including vorinostat, fludroxycortide, oxolinic acid, and flutamide) might be effective and efficient in alleviating or reversing the status of severe hypoxia and poor infiltration of immune cells. Conclusion: Our constructed prognostic model, based on hypoxia-immune-related genes, has excellent effectiveness and clinical application value. Moreover, some small-molecule drugs are screened to alleviate severe hypoxia and poor infiltration of immune cells.
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Affiliation(s)
- Shuheng Bai
- Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ling Chen
- Department of Chemotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yanli Yan
- Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xuan Wang
- Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Aimin Jiang
- Department of Chemotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Rong Li
- Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Haojing Kang
- Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhaode Feng
- Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Guangzu Li
- Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Wen Ma
- Medical School, Xi’an Jiaotong University Xi’an, Xi’an, China
| | - Jiangzhou Zhang
- Medical School, Xi’an Jiaotong University Xi’an, Xi’an, China
| | - Juan Ren
- Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Development of an Autophagy-Related Gene Prognostic Model and Nomogram for Estimating Renal Clear Cell Carcinoma Survival. JOURNAL OF ONCOLOGY 2021; 2021:8810849. [PMID: 33679977 PMCID: PMC7910047 DOI: 10.1155/2021/8810849] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 12/29/2020] [Accepted: 01/24/2021] [Indexed: 02/06/2023]
Abstract
Background Kidney renal clear cell carcinoma (KIRC) is a fatal malignancy of the urinary system. Autophagy is implicated in KIRC occurrence and development. Here, we evaluated the prognostic value of autophagy-related genes (ARGs) in kidney renal clear cell carcinoma. Materials and Methods We analyzed RNA sequencing and clinical KIRC patient data obtained from TCGA and ICGC to develop an ARG prognostic signature. Differentially expressed ARGs were further evaluated by functional assessment and bioinformatic analysis. Next, ARG score was determined in 215 KIRC patients using univariable Cox and LASSO regression analyses. An ARG nomogram was built based on multivariable Cox analysis. The prognosis nomogram model based on the ARG signatures and clinicopathological information was evaluated for discrimination, calibration, and clinical usefulness. Results A total of 47 differentially expressed ARGs were identified. Of these, 8 candidates that significantly correlated with KIRC overall survival were subjected to LASSO analysis and an ARG score built. Functional enrichment and bioinformatic analysis were used to reveal the differentially expressed ARGs in cancer-related biological processes and pathways. Multivariate Cox analysis was used to integrate the ARG nomogram with the ARG signature and clinicopathological information. The nomogram exhibited proper calibration and discrimination (C-index = 0.75, AUC = >0.7). Decision curve analysis also showed that the nomogram was clinically useful. Conclusions KIRC patients and doctors could benefit from ARG nomogram use in clinical practice.
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Chen Q, Hu L, Chen K. Construction of a Nomogram Based on a Hypoxia-Related lncRNA Signature to Improve the Prediction of Gastric Cancer Prognosis. Front Genet 2020; 11:570325. [PMID: 33193668 PMCID: PMC7641644 DOI: 10.3389/fgene.2020.570325] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 09/29/2020] [Indexed: 12/24/2022] Open
Abstract
Background Gastric cancer is one of the most common malignant tumors and has a poor prognosis. Hypoxia is related to the poor prognosis of cancer patients. We searched for hypoxia-related long non-coding RNAs (lncRNAs) to predict both overall survival (OS) and disease-free survival (DFS) of gastric cancer patients. Methods We obtained hypoxia-related lncRNA expression profiles and clinical follow-up data of patients with gastric cancer from The Cancer Genome Atlas and the Molecular Signatures Database. The patients were randomly divided into a training group, test group and combined group. The hypoxia-related prognostic signature was constructed by Lasso regression and Cox regression models, the prognoses in different groups were compared by Kaplan-Meier (K-M) analysis, and the accuracy of the prognostic model was assessed by receiver operating characteristic (ROC) analysis. Results A hypoxia-related prognostic signature comprising 10 lncRNAs was constructed to predict both OS and DFS in gastric cancer. In the training, test and combined groups, patients were divided into high- and low-risk groups according to the formula. Kaplan-Meier analysis showed that patients in the high-risk group have poor prognoses, and the difference was significant in the subgroup analyses. Receiver operating characteristic analysis revealed that the predictive power of the model prediction is more accurate than that of standard benchmarks. The signature differed across Helicobacter pylori (Hp) status and T stages. Multivariate Cox analysis showed that the signature is an independent risk factor for both OS and DFS. A clinically predictive nomogram combining the lncRNA signature and clinical features was constructed; the nomogram accurately predicted both OS and DFS and had high clinical application value. Weighted correlation network analysis combined with enrichment analysis showed that the primary pathways were the PI3K-Akt, JAK-STAT, and IL-17 signaling pathways. The target genes NOX4, COL8A1, and CHST1 were associated with poor prognosis in the Gene Expression Profiling Interactive Analysis, Gene Expression Omnibus, and K-M Plotter databases. Conclusions Our 10-lncRNA prognostic signature and nomogram are accurate, reliable tools for predicting both OS and DFS in gastric cancer.
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Affiliation(s)
- Qian Chen
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Lang Hu
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Kaihua Chen
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
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Sun KK, Wang QH, Wu YY. Challenges surrounding postoperative adjuvant chemotherapy for T2N0 gastric cancer. Oncol Lett 2020; 20:126. [PMID: 32934695 DOI: 10.3892/ol.2020.11985] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 07/23/2020] [Indexed: 02/06/2023] Open
Abstract
Determining the requirement for adjuvant chemotherapy in patients with stage IB gastric cancer (GC), and particularly for those with stage T2N0 (muscularis propria) disease, remains challenging. Patients with stage II/III disease benefit from postoperative adjuvant therapy; however, the randomized trials examining whether such therapy affords any survival benefit to patients with T2N0 disease are not sufficient. Current evidence suggests that not all patients with T2N0 disease should undergo such treatment, but only those with a high risk. To date, a number of retrospective studies have attempted to identify factors that are predictive of increased risk in an effort to guide adjuvant therapy-related clinical decision making. The National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology have published guidelines regarding factors associated with increased patient risk. As a result, treatment decisions for patients with stage T2N0 disease are currently determined on an individualized basis, in light of risk factors and the potential benefits of treatment. The present review surveyed current evidence related to the treatment of patients with high-risk GC and highlighted the potential avenues for future investigated.
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Affiliation(s)
- Ke-Kang Sun
- Department of Gastrointestinal Surgery, Affiliated Kunshan Hospital to Jiangsu University, Suzhou, Jiangsu 215300, P.R. China.,Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215008, P.R. China
| | - Qing-Hua Wang
- Department of Gastrointestinal Surgery, Affiliated Kunshan Hospital to Jiangsu University, Suzhou, Jiangsu 215300, P.R. China
| | - Yong-You Wu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215008, P.R. China
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Shi M, Zhou B, Yang SP. Nomograms for predicting overall survival and cancer-specific survival in young patients with pancreatic cancer in the US based on the SEER database. PeerJ 2020; 8:e8958. [PMID: 32322444 PMCID: PMC7164422 DOI: 10.7717/peerj.8958] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 03/22/2020] [Indexed: 12/12/2022] Open
Abstract
Background The incidence of young patients with pancreatic cancer (PC) is on the rise, and there is a lack of models that could effectively predict their prognosis. The purpose of this study was to construct nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of young patients with PC. Methods PC patients younger than 50 years old from 2004 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were selected and randomly divided into training set and validation set. Univariable and forward stepwise multivariable Cox analysis was used to determine the independent factors affecting OS. The Fine and Gray competing risk regression model was used to determine the independent factors affecting CSS. We used significant variables in the training set to construct nomograms predicting prognosis. The discrimination and calibration power of models were evaluated by concordance index (C-index), calibration curve and 10-flod cross-validation. Results A total of 4,146 patients were selected. Multivariable Cox analysis showed that gender, race, grade, pathological types, AJCC stage and surgery were independent factors affecting OS. The C-index of the nomogram predicting OS in training and validation was 0.733 (average = 0.731, 95% CI [0.724–0.738]) and 0.742 (95% CI [0.725–0.759]), respectively. Competing risk analysis showed that primary site, pathological types, AJCC stage and surgery were independent factors affecting CSS. The C-index of the nomogram predicting CSS in training and validation set was 0.792 (average = 0.765, 95% CI [0.742–0.788]) and 0.776 (95% CI [0.773–0.779]), respectively. C-index based on nomogram was better in training and validation set than that based on AJCC stage. Calibration curves showed that these nomograms could accurately predict the 1-, 3- and 5-year OS and CSS both in training set and validation set. Conclusions The nomograms could effectively predict OS and CSS in young patients with PC, which help clinicians more accurately and quantitatively judge the prognosis of individual patients.
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Affiliation(s)
- Min Shi
- Department of Gastroenterology, Liyang Branch of Jiangsu Province Hospital, Liyang, China
| | - Biao Zhou
- Department of Gastroenterology, Liyang Branch of Jiangsu Province Hospital, Liyang, China
| | - Shu-Ping Yang
- Department of Gastroenterology, Liyang Branch of Jiangsu Province Hospital, Liyang, China
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A DNA methylation signature to improve survival prediction of gastric cancer. Clin Epigenetics 2020; 12:15. [PMID: 31959204 PMCID: PMC6972030 DOI: 10.1186/s13148-020-0807-x] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 01/02/2020] [Indexed: 02/08/2023] Open
Abstract
Background The current Union International Committee on Cancer or the American Joint Committee on Cancer TNM stage system has shown valuable but insufficient estimation for subsets of gastric cancer and prediction for prognosis patients. Thus, there is an urgent need to identify diagnostic, prognostic, and predictive biomarkers to improve patients’ outcomes. Our aim was to perform an integrative analysis on publicly available datasets to identify epigenetic changes that may play key role in the initiation and progression of gastric cancer, based on which we set to develop a DNA methylation signature to improve survival prediction of gastric cancer. Results A total of 340 methylation-related differentially expression genes (mrDEGs) were screened in gastric cancer patients from The Cancer Genome Atlas (TCGA) project. Pathway enrichment analysis revealed that they were involved in the biological process related to initiation and progression of gastric cancer. Based on the mrDEGs identified, we developed a DNA methylation signature consisting of ten gene members (SCNN1B, NFE2L3, CLDN2, RBPMS2, JPH2, GBP6, COL4A5, SMKR1, PPP1R14A, and ARL4D) according to their methylation β value. This innovative DNA methylation signature was associated with cancer recurrence, while it showed independence of cancer recurrence and TNM stage for survival prediction. Combination of this DNA methylation signature and TNM stage improved overall survival prediction in the receiver operating characteristic analysis. We also verified that two individual genes (PPP1R14A and SCNN1B) of the identified prognostic signature were regulated by promoter region methylation in a panel of gastric cell lines. Conclusions This study presents a powerful DNA methylation signature by performing analyses integrating multi-source data including transcriptome, methylome, and clinical outcome of gastric cancer patients from TCGA. The identified DNA methylation signature may be used to refine the current prognostic model and facilitate further stratification of patients in the future clinical trials. Further experimental studies are warranted to unveil the regulatory mechanism and functional role of all the individual genes of the DNA methylation signature. Also, clinical investigations in large GC patient cohorts are greatly needed to validate our findings.
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Jiang L, Zhao XH, Mao YL, Wang JF, Zheng HJ, You QS. Long non-coding RNA RP11-468E2.5 curtails colorectal cancer cell proliferation and stimulates apoptosis via the JAK/STAT signaling pathway by targeting STAT5 and STAT6. J Exp Clin Cancer Res 2019; 38:465. [PMID: 31718693 PMCID: PMC6852742 DOI: 10.1186/s13046-019-1428-0] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 09/23/2019] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) are tumor-associated biological molecules and have been found to be implicated in the progression of colorectal cancer (CRC). This study aims to examine the effects of lncRNA RP11-468E2.5 and its target genes (STAT5 and STAT6) on the biological activities of CRC cells via the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway. METHODS We initially screened the GEO database for differentially expressed lncRNAs related to CRC and then made a prediction of the implicated target genes. Then we collected CRC tissues and adjacent normal tissues from 169 CRC patients. Human CRC HCT116 and SW480 cells were treated with small interference RNA (siRNA) against RP11-468E2.5, AG490 (an inhibitor of the JAK/STAT signaling pathway), or both in combination. Next, we measured the effects of RP11-468E2.5 treatment on cellular activities such as cell viability, cycle distribution and cell apoptosis, and studied interactions among RP11-468E2.5, STAT5/STAT6, and the JAK/STAT signaling pathway. Finally, an in vivo tumor formation assay was performed to observe the effect of RP11-468E2.5 on tumor growth. RESULTS The CRC-related gene microarray data showed low expression of RP11-468E2.5 in CRC surgical specimens. However, RP11-468E2.5 was confirmed to target STAT5 and STAT6, which participate in the JAK/STAT signaling pathway. CRC tissues showed lower expression of RP11-468E2.5, higher expression of STAT5, STAT6 and of the cell cycle marker Cyclin D1 (CCND1), compared to the findings in adjacent normal tissues. The treatment of siRNA against RP11-468E2.5 increased expression of JAK2, STAT3, STAT5, STAT6, CCND1 and Bcl-2 along with the extent of STAT3, STAT5 and STAT6 phosphorylation, while lowering expression of P21 and P27. Treatment with AG490 exhibited approximately opposite effects, whereas siRNA against RP11-468E2.5 treatment stimulated CRC cell proliferation and reduced cell apoptosis, while promoting cell cycle entry; AG490 treatment reversed these results. CONCLUSIONS Altogether, we conclude that up-regulation of RP11-468E2.5 inhibits the JAK/STAT signaling pathway by targeting STAT5 and STAT6, thereby suppressing cell proliferation and promoting cell apoptosis in CRC.
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Affiliation(s)
- Li Jiang
- Department of Hematology and Lymphatic Diseases, Harbin Medical University Tumour Hospital, Harbin, 150081, People's Republic of China
| | - Xu-Hai Zhao
- Department of Breast Surgery, Harbin Medical University Tumour Hospital, Harbin, 150081, People's Republic of China
| | - Yin-Ling Mao
- Department of Abdominal Radiotherapy, Harbin Medical University Tumour Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, People's Republic of China.
| | - Jun-Feng Wang
- Department of Thoracic Surgery, Harbin Medical University Tumour Hospital, Harbin, 150081, People's Republic of China
| | - Hui-Jun Zheng
- Department of General Surgery, Kangying Hospital of Mingshui County, Suihua, 151700, People's Republic of China
| | - Qing-Shan You
- Department of Abdominal Radiotherapy, Harbin Medical University Tumour Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, People's Republic of China
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12
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Zhang W, Zhangyuan G, Wang J, Jin K, Liu Y, Wang F, Yu W, Zhang H, Li G, Yu D, Chen H, Xu Q, Sun B. Effect of lymph nodes count in node-positive gastric cancer. J Cancer 2019; 10:5646-5653. [PMID: 31737101 PMCID: PMC6843880 DOI: 10.7150/jca.30979] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 08/15/2019] [Indexed: 02/07/2023] Open
Abstract
Background: The retrieved lymph node (LN) count has been confirmed as a prognostic indicator in various cancers. However, the correlation between LN counts and patient prognosis in gastric cancer with node-positive is not fully studied. Methods: A total of 8475 patients undergoing gastrectomy in Surveillance, Epidemiology, and End Results Program (SEER)-registered gastric cancer were analyzed. Kaplan-Meier methods and multivariable Cox regression models were used to analyze long-term outcomes and risk factors. Moreover, nomograms including LN counts were established to predict overall survival (OS) and cancer-specific survival (CSS), and Harrell's concordance index (c-index) was adopted to evaluate prediction accuracy. Results: Patients were stratified into 1-6, 7-14, and > 14 subgroups according to the optimal cutoff for retrieved LNs in terms of 5-year CSS. Further analysis indicated that higher LN counts were an independent predictor of longer survival in each N category. Nomograms on CSS and OS were established according to all significant factors, and c-indexes were 0.663 and 0.654 (P< 0.001), respectively. Conclusions: These results indicated that the more the LNs retrieved, the better the survival would be. Nomograms incorporating LN counts can be recommended as practical models to provide more accurate prognostic information for GC patients.
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Affiliation(s)
- Wenjie Zhang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
- Department of Hepatobiliary Surgery of Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China
| | - Guangyan Zhangyuan
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China
| | - Jincheng Wang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
- Department of Hepatobiliary Surgery of Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China
| | - Kangpeng Jin
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
| | - Yang Liu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
- Department of Hepatobiliary Surgery of Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Fei Wang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
- Department of Hepatobiliary Surgery of Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Weiwei Yu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
- Department of Hepatobiliary Surgery of Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Haitian Zhang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
- Department of Hepatobiliary Surgery of Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Guoqiang Li
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
| | - Decai Yu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
| | - Huihui Chen
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
| | - Qingxiang Xu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
- Department of Hepatobiliary Surgery of Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Beicheng Sun
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210029, Jiangsu Province, P.R. China
- Department of Hepatobiliary Surgery of Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, P.R. China
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Lin JX, Lin JP, Li P, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Lin M, Tu RH, Zheng CH, Huang CM. New metastatic lymph node classification for early gastric cancer should differ from those for advanced gastric adenocarcinoma: Results based on the SEER database. World J Clin Cases 2019; 7:145-155. [PMID: 30705892 PMCID: PMC6354097 DOI: 10.12998/wjcc.v7.i2.145] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 11/13/2018] [Accepted: 11/23/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To establish an appropriate N classification system for early gastric cancer (EGC). METHODS Data from 10714 patients who underwent radical gastrectomy between 1988 and 2011 were retrieved from the National Cancer Institute's Surveillance, Epidemiology, and End Result database. The overall survival (OS) based on the eighth edition and new tumor lymph node metastasis (TNM) staging systems were compared, and the analysis was repeated in an external validation set from the Fujian Medical University Union Hospital database. RESULTS There were no significant differences in OS between N1 and N2 cancers or between N3a and N3b cancers in cases of EGC. The X-tile program identified that the new staging system for EGC consisted of T1N0, T1N1' [1-6 metastatic lymph nodes (LNs)], and T1N2' ( ≥ 7 metastatic LNs). Compared with the eighth edition of the TNM staging system, the OS of patients in T1N1' stage was similar to that of patients with stage IIA disease, whereas the OS of patients in T1N2' stage was similar to that of patients with stage IIB disease. The new TNM staging system exhibited a slightly lower Akaike Information Criterion value and higher χ 2 and c-statistic compared with the eighth edition of the TNM classification system. Similar results were found in the external validation dataset from the external validation set. CONCLUSION We have developed an optional new TNM staging system with a better predictive ability that can be used to accurately predict the 5-year OS of patients with EGC.
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Affiliation(s)
- Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Jia-bin Wang, Chang-Ming Huang, Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
| | - Jun-Peng Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Jia-bin Wang, Chang-Ming Huang, Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
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14
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Yang Y, Qu A, Zhao R, Hua M, Zhang X, Dong Z, Zheng G, Pan H, Wang H, Yang X, Zhang Y. Genome-wide identification of a novel miRNA-based signature to predict recurrence in patients with gastric cancer. Mol Oncol 2018; 12:2072-2084. [PMID: 30242969 PMCID: PMC6275280 DOI: 10.1002/1878-0261.12385] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 08/21/2018] [Accepted: 09/11/2018] [Indexed: 12/21/2022] Open
Abstract
The current tumor node metastasis (TNM) staging system is inadequate for identifying high-risk gastric cancer (GC) patients. Using a systematic and comprehensive-biomarker discovery and validation approach, we attempted to build a microRNA (miRNA)-recurrence classifier (MRC) to improve the prognostic prediction of GC. We identified 312 differentially expressed miRNAs in 446 GC tissues compared to 45 normal controls by analyzing high-throughput data from The Cancer Genome Atlas (TCGA). Using a Cox regression model, we developed an 11-miRNA signature that could successfully discriminate high-risk patients in the training set (n = 372; P < 0.0001). Quantitative real-time polymerase chain reaction-based validation in an independent clinical cohort (n = 88) of formalin-fixed paraffin-embedded clinical GC samples showed that MRC-derived high-risk patients succumb to significantly poor recurrence-free survival in GC patients (P < 0.0001). Cox and stratification analysis indicated that the prognostic value of this signature was independent of clinicopathological risk factors. Time-dependent receiver operating characteristic (ROC) analysis revealed that the area under the curve of this signature was significantly larger than that of TNM stage in the TCGA (0.733 vs. 0.589 at 3 years, P = 0.004; 0.802 vs. 0.635 at 5 years, P = 0.005) and validation cohort (0.835 vs. 0.689 at 3 years, P = 0.003). A nomogram was constructed for clinical use, which integrated both MRC and clinical-related variables (depth of invasion, lymph node status and distance metastasis) and did well in the calibration plots. In conclusion, this novel miRNA-based signature is superior to currently used clinicopathological features for identifying high-risk GC patients. It can be readily translated into clinical practice with formalin-fixed paraffin-embedded specimens for specific decision-making applications.
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Affiliation(s)
- Yongmei Yang
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, China
| | - Ailin Qu
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, China
| | - Rui Zhao
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, China
| | - Mengmeng Hua
- Department of Oral Pathology, Institute of Stomatology, Qilu Hospital, Shandong University, Jinan, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, China
| | - Zhaogang Dong
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, China
| | - Guixi Zheng
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, China
| | - Hongwei Pan
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, China
| | - Hongchun Wang
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, China
| | - Xiaoyun Yang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, China
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15
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Cheng P. A prognostic 3‐long noncoding RNA signature for patients with gastric cancer. J Cell Biochem 2018; 119:9261-9269. [DOI: 10.1002/jcb.27195] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 05/24/2018] [Indexed: 12/27/2022]
Affiliation(s)
- Peng Cheng
- Department of Internal Medicine‐Oncology The First Affiliated Hospital of Nanyang Medical College Nanyang China
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16
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Virgilio E, Giarnieri E, Giovagnoli MR, Montagnini M, Proietti A, D'Urso R, Nigri G, Mercantini P, Ramacciato G, Cavallini M, Balducci G. Presence of cancer cells in gastric lavage of gastric cancer patients as an indicator of advanced disease, predictor of tumour aggressive phenotype and independent prognostic factor for poor survival: The endoluminal metastatic pathway of gastric cancer and GL0/GL1 classification. Cytopathology 2017; 29:41-48. [PMID: 29063636 DOI: 10.1111/cyt.12484] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2017] [Indexed: 01/20/2023]
Abstract
OBJECTIVE As of 2017, the pathobiology of gastric cancer (GC) is far from fully understood; consequently, new methods of basic and advanced research have been proposed and tested. The presence (GL1) vs absence (GL0) of malignant cells exfoliated in gastric lavage (GL) of GC patients was formerly evaluated with diagnostic intent but not for staging or prognostic assessment. We investigated this hitherto unreported application of cytopathology. METHODS GL was preoperatively and prospectively collected from 80 GC patients and cytologically analysed. The results were compared with the classic clinicopathological features of GC and related to survival. The prognostic value of GL1 was assessed through univariate and multivariate analyses. RESULTS GL1 was detected in 36 samples (45%) and correlated with advanced tumour depth (T3-T4), lymphatic metastasis (N+), distant metastasis (M1) and lymphovascular invasion (LVI1; P=.0317, .0024, .003 and .0028, respectively). Overall survival (OS) was significantly shorter for GL1 (23 months) vs GL0 patients (42 months; P=.005) and GL1 vs GL0 T1 subjects (12.6 vs 47.8 months, P=.0029). Univariate analysis revealed that GL1, N+, M1, LVI1 and advanced stage were significantly associated with OS. Multivariate analysis assessed GL1 as the only independent prognostic factor for worse OS and progression-free survival (P=.0013 and .0107). CONCLUSIONS In the present study, GL1 was correlated with advanced disease, aggressive tumour behaviour and poor prognosis. Although additional studies are needed to confirm these findings, the GL0/GL1 classification can be applied to GC patients to achieve higher accuracy in staging, prognostic stratification and treatment selection.
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Affiliation(s)
- E Virgilio
- Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - E Giarnieri
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - M R Giovagnoli
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - M Montagnini
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - A Proietti
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - R D'Urso
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - G Nigri
- Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - P Mercantini
- Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - G Ramacciato
- Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - M Cavallini
- Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
| | - G Balducci
- Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University "Sapienza", St. Andrea Hospital, Rome, Italy
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