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An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer

Increasing evidence has indicated that current tumor-node-metastasis (TNM) stage alone cannot predict prognosis and adjuvant chemotherapy benefits accurately for stages II and III gastric cancer (GC) patients after surgery. In order to improve the predictive ability of survival and adjuvant chemothe...

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Autores principales: Yan, Hongfei, Chen, Yang, Yang, Zichang, Li, Zhi, Che, Xiaofang, Xiao, Jiawen, Liu, Yunpeng, Qu, Xiujuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890018/
https://www.ncbi.nlm.nih.gov/pubmed/33613554
http://dx.doi.org/10.3389/fimmu.2020.621623
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author Yan, Hongfei
Chen, Yang
Yang, Zichang
Li, Zhi
Che, Xiaofang
Xiao, Jiawen
Liu, Yunpeng
Qu, Xiujuan
author_facet Yan, Hongfei
Chen, Yang
Yang, Zichang
Li, Zhi
Che, Xiaofang
Xiao, Jiawen
Liu, Yunpeng
Qu, Xiujuan
author_sort Yan, Hongfei
collection PubMed
description Increasing evidence has indicated that current tumor-node-metastasis (TNM) stage alone cannot predict prognosis and adjuvant chemotherapy benefits accurately for stages II and III gastric cancer (GC) patients after surgery. In order to improve the predictive ability of survival and adjuvant chemotherapy benefits of GC patients after surgery, this study aimed to establish an immune signature based on the composition of infiltrating immune cells. Twenty-eight types of immune cell fractions were evaluated based on the expression profiles of GC patients from the Gene Expression Omnibus (GEO) database using single-sample gene set enrichment analysis (ssGSEA). The immunoscore (IS) was constructed using a least absolute shrinkage and selection operator (LASSO) Cox regression model. Through the LASSO model, an IS classifier consisting of eight immune cells was constructed. Significant difference was found between high-IS and low-IS groups in the training cohort in disease-free survival (DFS, P < 0.0001) and overall survival (OS, P < 0.0001). Multivariate analysis showed that the IS classifier was an independent prognostic indicator. Moreover, a combination of IS and TNM stage exhibited better prognostic value than TNM stage alone. Further analysis demonstrated that low-IS patients who had more tumor-infiltrating lymphocytes had better response to adjuvant chemotherapy. More importantly, we found that patients with high-IS were more likely to benefit from a Xeloda plus cisplatin regimen after surgery. Finally, we established two nomograms to screen the stage II and III GC patients who benefitted from adjuvant chemotherapy after surgery. The combination of IS classifier and TNM stage could predict DFS and OS of GC patients. The IS model has been proven as a promising tool that can be used to identify the patients with stages II and III GC who may benefit from adjuvant chemotherapy.
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spelling pubmed-78900182021-02-19 An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer Yan, Hongfei Chen, Yang Yang, Zichang Li, Zhi Che, Xiaofang Xiao, Jiawen Liu, Yunpeng Qu, Xiujuan Front Immunol Immunology Increasing evidence has indicated that current tumor-node-metastasis (TNM) stage alone cannot predict prognosis and adjuvant chemotherapy benefits accurately for stages II and III gastric cancer (GC) patients after surgery. In order to improve the predictive ability of survival and adjuvant chemotherapy benefits of GC patients after surgery, this study aimed to establish an immune signature based on the composition of infiltrating immune cells. Twenty-eight types of immune cell fractions were evaluated based on the expression profiles of GC patients from the Gene Expression Omnibus (GEO) database using single-sample gene set enrichment analysis (ssGSEA). The immunoscore (IS) was constructed using a least absolute shrinkage and selection operator (LASSO) Cox regression model. Through the LASSO model, an IS classifier consisting of eight immune cells was constructed. Significant difference was found between high-IS and low-IS groups in the training cohort in disease-free survival (DFS, P < 0.0001) and overall survival (OS, P < 0.0001). Multivariate analysis showed that the IS classifier was an independent prognostic indicator. Moreover, a combination of IS and TNM stage exhibited better prognostic value than TNM stage alone. Further analysis demonstrated that low-IS patients who had more tumor-infiltrating lymphocytes had better response to adjuvant chemotherapy. More importantly, we found that patients with high-IS were more likely to benefit from a Xeloda plus cisplatin regimen after surgery. Finally, we established two nomograms to screen the stage II and III GC patients who benefitted from adjuvant chemotherapy after surgery. The combination of IS classifier and TNM stage could predict DFS and OS of GC patients. The IS model has been proven as a promising tool that can be used to identify the patients with stages II and III GC who may benefit from adjuvant chemotherapy. Frontiers Media S.A. 2021-02-04 /pmc/articles/PMC7890018/ /pubmed/33613554 http://dx.doi.org/10.3389/fimmu.2020.621623 Text en Copyright © 2021 Yan, Chen, Yang, Li, Che, Xiao, Liu and Qu 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 Immunology
Yan, Hongfei
Chen, Yang
Yang, Zichang
Li, Zhi
Che, Xiaofang
Xiao, Jiawen
Liu, Yunpeng
Qu, Xiujuan
An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer
title An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer
title_full An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer
title_fullStr An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer
title_full_unstemmed An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer
title_short An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer
title_sort immune cell signature is associated with disease-free survival and adjuvant chemosensitivity of patients with resectable gastric cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890018/
https://www.ncbi.nlm.nih.gov/pubmed/33613554
http://dx.doi.org/10.3389/fimmu.2020.621623
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