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Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer

Tumor-infiltrating lymphocytes (TILs) in gastric cancer are closely related to clinical prognosis; however, little is known regarding the immune microenvironment in this disease. Thus, RNA-sequencing data from gastric cancer patients were downloaded from the Gene Expression Omnibus (GEO). The propor...

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Autores principales: Xie, Siyuan, Mo, Pingfan, Li, Ning, Cai, Wen, Ruan, Jingjing, Ye, Jun, Mao, Jianshan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561394/
https://www.ncbi.nlm.nih.gov/pubmed/33117674
http://dx.doi.org/10.3389/fonc.2020.522015
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author Xie, Siyuan
Mo, Pingfan
Li, Ning
Cai, Wen
Ruan, Jingjing
Ye, Jun
Mao, Jianshan
author_facet Xie, Siyuan
Mo, Pingfan
Li, Ning
Cai, Wen
Ruan, Jingjing
Ye, Jun
Mao, Jianshan
author_sort Xie, Siyuan
collection PubMed
description Tumor-infiltrating lymphocytes (TILs) in gastric cancer are closely related to clinical prognosis; however, little is known regarding the immune microenvironment in this disease. Thus, RNA-sequencing data from gastric cancer patients were downloaded from the Gene Expression Omnibus (GEO). The proportion of immune cells was determined based on a deconvolution algorithm (CIBERSORT), and gene expression profiles were analyzed in the context of clinical outcomes to construct an immune risk score. Data were analyzed using least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression, to identify prognostic markers of gastric cancer survival. The model included four immune cell types: neutrophils, plasma cells, activated CD4(+) memory T cells, and T follicular helper cells. Patients were classified into two subgroups based on risk score, and a significant difference in overall survival (OS) was seen between the subgroups in both the training and testing cohorts, particularly in patients with tumor stages ≥T3. Multivariable analysis revealed that both T-stage and risk score were independent prognostic factors for gastric cancer survival [hazard ratio (HR) 1.505; 95% confidence interval (CI) 1.043–2.173, HR 1.686; 95% CI 1.367–2.080]. Risk scores and clinical factors were then integrated into a nomogram to build a model with both good discriminatory power and accuracy in predicting clinical outcomes. Further analysis using gene set enrichment analysis (GSEA) identified strong associations of immune risk with TGF-β and tumor metastasis-related pathways, which could inform research on the molecular mechanisms of gastric cancer. Collectively, the data presented here suggest that an immune risk model can make an important contribution to predictions prognosis in gastric cancer patients.
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spelling pubmed-75613942020-10-27 Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer Xie, Siyuan Mo, Pingfan Li, Ning Cai, Wen Ruan, Jingjing Ye, Jun Mao, Jianshan Front Oncol Oncology Tumor-infiltrating lymphocytes (TILs) in gastric cancer are closely related to clinical prognosis; however, little is known regarding the immune microenvironment in this disease. Thus, RNA-sequencing data from gastric cancer patients were downloaded from the Gene Expression Omnibus (GEO). The proportion of immune cells was determined based on a deconvolution algorithm (CIBERSORT), and gene expression profiles were analyzed in the context of clinical outcomes to construct an immune risk score. Data were analyzed using least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression, to identify prognostic markers of gastric cancer survival. The model included four immune cell types: neutrophils, plasma cells, activated CD4(+) memory T cells, and T follicular helper cells. Patients were classified into two subgroups based on risk score, and a significant difference in overall survival (OS) was seen between the subgroups in both the training and testing cohorts, particularly in patients with tumor stages ≥T3. Multivariable analysis revealed that both T-stage and risk score were independent prognostic factors for gastric cancer survival [hazard ratio (HR) 1.505; 95% confidence interval (CI) 1.043–2.173, HR 1.686; 95% CI 1.367–2.080]. Risk scores and clinical factors were then integrated into a nomogram to build a model with both good discriminatory power and accuracy in predicting clinical outcomes. Further analysis using gene set enrichment analysis (GSEA) identified strong associations of immune risk with TGF-β and tumor metastasis-related pathways, which could inform research on the molecular mechanisms of gastric cancer. Collectively, the data presented here suggest that an immune risk model can make an important contribution to predictions prognosis in gastric cancer patients. Frontiers Media S.A. 2020-09-30 /pmc/articles/PMC7561394/ /pubmed/33117674 http://dx.doi.org/10.3389/fonc.2020.522015 Text en Copyright © 2020 Xie, Mo, Li, Cai, Ruan, Ye and Mao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Xie, Siyuan
Mo, Pingfan
Li, Ning
Cai, Wen
Ruan, Jingjing
Ye, Jun
Mao, Jianshan
Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer
title Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer
title_full Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer
title_fullStr Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer
title_full_unstemmed Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer
title_short Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer
title_sort tumor-infiltrating lymphocyte-based risk score for predicting prognosis in gastric cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561394/
https://www.ncbi.nlm.nih.gov/pubmed/33117674
http://dx.doi.org/10.3389/fonc.2020.522015
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