Development and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer

Objective. Due to the molecular heterogeneity of gastric cancer, only minor patients respond to immunotherapeutic schemes. This study is aimed at developing an immune-based gene signature for risk stratification and immunotherapeutic efficacy assessment in gastric cancer. Methods. An immune-based ge...

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Autores principales:	Feng Qiu, Yumei Zhu, Yafeng Shi, Jingjing Ji, Yingchao Jin
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/909b07ac07744e1bb3896875db260a51
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spelling	oai:doaj.org-article:909b07ac07744e1bb3896875db260a512021-11-22T01:10:29ZDevelopment and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer1875-863010.1155/2021/4251763https://doaj.org/article/909b07ac07744e1bb3896875db260a512021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/4251763https://doaj.org/toc/1875-8630Objective. Due to the molecular heterogeneity of gastric cancer, only minor patients respond to immunotherapeutic schemes. This study is aimed at developing an immune-based gene signature for risk stratification and immunotherapeutic efficacy assessment in gastric cancer. Methods. An immune-based gene signature was developed in gastric cancer by LASSO method in the training set. The predictive performance was validated in the external datasets. KEGG pathways related to risk scores were assessed by GSEA. Based on multivariate Cox regression analysis, a nomogram was established. Sensitivity to chemotherapy drugs was evaluated between high- and low-risk samples. The relationships of risk scores with infiltration levels of immune cells, stromal scores, immune scores, immune cell subgroups, and overall response to anti-PD-L1 therapy were determined. Results. Our results showed that high risk scores were indicative of undesirable survival outcomes both in the training set (p<0.0001) and the validation set (p=0.002). Moreover, this signature could independently predict patients’ survival (HR: 2.656 (1.919-3.676) and p<0.001). Subgroup analysis confirmed the sensitivity of this signature in predicting prognosis (all p<0.05). Cancer-related pathways were primarily enriched in high-risk samples, such as MAPK and TGF-β pathways (p<0.05). By incorporating stage and the risk score, we established a nomogram for predicting one-, three-, and five-year survival probability. Patients with high-risk scores were more sensitive to chemotherapy drugs (p<0.05). There was heterogeneity in immune cells between high- and low-risk samples (p<0.05). Samples with progressive disease exhibited the highest risk score, and those with complete response had the lowest risk score (p<0.05). Conclusion. This immune-based gene signature might be representative of a promising prognostic classifier for predicting risk stratification and immunotherapeutic efficacy in gastric cancer, assisting personalized therapy and follow-up plan.Feng QiuYumei ZhuYafeng ShiJingjing JiYingchao JinHindawi LimitedarticleMedicine (General)R5-920ENDisease Markers, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Feng Qiu Yumei Zhu Yafeng Shi Jingjing Ji Yingchao Jin Development and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer
description	Objective. Due to the molecular heterogeneity of gastric cancer, only minor patients respond to immunotherapeutic schemes. This study is aimed at developing an immune-based gene signature for risk stratification and immunotherapeutic efficacy assessment in gastric cancer. Methods. An immune-based gene signature was developed in gastric cancer by LASSO method in the training set. The predictive performance was validated in the external datasets. KEGG pathways related to risk scores were assessed by GSEA. Based on multivariate Cox regression analysis, a nomogram was established. Sensitivity to chemotherapy drugs was evaluated between high- and low-risk samples. The relationships of risk scores with infiltration levels of immune cells, stromal scores, immune scores, immune cell subgroups, and overall response to anti-PD-L1 therapy were determined. Results. Our results showed that high risk scores were indicative of undesirable survival outcomes both in the training set (p<0.0001) and the validation set (p=0.002). Moreover, this signature could independently predict patients’ survival (HR: 2.656 (1.919-3.676) and p<0.001). Subgroup analysis confirmed the sensitivity of this signature in predicting prognosis (all p<0.05). Cancer-related pathways were primarily enriched in high-risk samples, such as MAPK and TGF-β pathways (p<0.05). By incorporating stage and the risk score, we established a nomogram for predicting one-, three-, and five-year survival probability. Patients with high-risk scores were more sensitive to chemotherapy drugs (p<0.05). There was heterogeneity in immune cells between high- and low-risk samples (p<0.05). Samples with progressive disease exhibited the highest risk score, and those with complete response had the lowest risk score (p<0.05). Conclusion. This immune-based gene signature might be representative of a promising prognostic classifier for predicting risk stratification and immunotherapeutic efficacy in gastric cancer, assisting personalized therapy and follow-up plan.
format	article
author	Feng Qiu Yumei Zhu Yafeng Shi Jingjing Ji Yingchao Jin
author_facet	Feng Qiu Yumei Zhu Yafeng Shi Jingjing Ji Yingchao Jin
author_sort	Feng Qiu
title	Development and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer
title_short	Development and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer
title_full	Development and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer
title_fullStr	Development and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer
title_full_unstemmed	Development and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer
title_sort	development and verification of an immune-based gene signature for risk stratification and immunotherapeutic efficacy assessment in gastric cancer
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/909b07ac07744e1bb3896875db260a51
work_keys_str_mv	AT fengqiu developmentandverificationofanimmunebasedgenesignatureforriskstratificationandimmunotherapeuticefficacyassessmentingastriccancer AT yumeizhu developmentandverificationofanimmunebasedgenesignatureforriskstratificationandimmunotherapeuticefficacyassessmentingastriccancer AT yafengshi developmentandverificationofanimmunebasedgenesignatureforriskstratificationandimmunotherapeuticefficacyassessmentingastriccancer AT jingjingji developmentandverificationofanimmunebasedgenesignatureforriskstratificationandimmunotherapeuticefficacyassessmentingastriccancer AT yingchaojin developmentandverificationofanimmunebasedgenesignatureforriskstratificationandimmunotherapeuticefficacyassessmentingastriccancer
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Development and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer

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