Immunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer

BackgroundAsians have the highest incidence of gastric cancer (GC), and the prognosis of Asian GC is poor. Furthermore, the therapeutics for Asian GC is limited because of genetic heterogeneity and screening difficulty at the early stage. This study aimed to develop an immune-related gene (IRG)-base...

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Autores principales:	Chenchen Mao, Liangliang Ma, Yingpeng Huang, Xinxin Yang, He Huang, Wentao Cai, Andriamifehimanjaka Sitrakiniaina, Ruihong Gu, Xiangyang Xue, Xian Shen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	gastric cancer Asian cancer immunomodulatory gene immunotherapy prognostic gene signature Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/64b2dd225a2f4a4388173d0f609f8ed8
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spelling	oai:doaj.org-article:64b2dd225a2f4a4388173d0f609f8ed82021-11-05T08:30:03ZImmunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer2234-943X10.3389/fonc.2021.750768https://doaj.org/article/64b2dd225a2f4a4388173d0f609f8ed82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.750768/fullhttps://doaj.org/toc/2234-943XBackgroundAsians have the highest incidence of gastric cancer (GC), and the prognosis of Asian GC is poor. Furthermore, the therapeutics for Asian GC is limited because of genetic heterogeneity and screening difficulty at the early stage. This study aimed to develop an immune-related gene (IRG)-based prognostic signature and to explore prognosis-related regulatory mechanism and therapeutic target for Asian GC.MethodsTo elucidate the prognostic value of IRGs in Asian GC, a comprehensive analysis of IRG expression profiles and overall survival times in 364 Asian GC patients from the Asian Cancer Research Group (ACRG) and The Cancer Genome Atlas (TCGA) databases was performed, and a novel prognostic index was established. To further explore regulatory prognosis mechanisms and therapeutic targets, a tumor immunogenomic landscape analysis, including stromal and immune subcomponents, cell types, panimmune gene sets, and immunomodulatory genes, was performed.ResultOur analysis allowed the creation of an optimal risk assessment model, the Asian-specific IRG-based prognostic index (ASIRGPI), which showed a high accuracy in predicting survival in Asian GC. We also developed an ASIRGPI-based nomogram to predict the 3- and 5-year overall survival (OS) of Asian GC patients. The impact of the ASIRGPI on the worse prognosis of Asian GC was possibly related to the stromal component remodeling. Specifically, TGFβ gene sets were significantly associated with the ASIRGPI and worse prognosis. Immunomodulatory gene analysis further revealed that TGFβ1 and EDNRB may be the novel potential therapeutic targets for Asian GC.ConclusionsAs a tumor microenvironment-relevant gene set-based prognostic signature, the ASIRGPI model provides an effective approach for evaluating the prognosis of Asian GC and may even prolong OS by enabling the selection of individualized therapy with the novel targets.Chenchen MaoLiangliang MaYingpeng HuangXinxin YangHe HuangWentao CaiAndriamifehimanjaka SitrakiniainaRuihong GuXiangyang XueXian ShenFrontiers Media S.A.articlegastric cancerAsian cancerimmunomodulatory geneimmunotherapyprognostic gene signatureNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gastric cancer Asian cancer immunomodulatory gene immunotherapy prognostic gene signature Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	gastric cancer Asian cancer immunomodulatory gene immunotherapy prognostic gene signature Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Chenchen Mao Liangliang Ma Yingpeng Huang Xinxin Yang He Huang Wentao Cai Andriamifehimanjaka Sitrakiniaina Ruihong Gu Xiangyang Xue Xian Shen Immunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer
description	BackgroundAsians have the highest incidence of gastric cancer (GC), and the prognosis of Asian GC is poor. Furthermore, the therapeutics for Asian GC is limited because of genetic heterogeneity and screening difficulty at the early stage. This study aimed to develop an immune-related gene (IRG)-based prognostic signature and to explore prognosis-related regulatory mechanism and therapeutic target for Asian GC.MethodsTo elucidate the prognostic value of IRGs in Asian GC, a comprehensive analysis of IRG expression profiles and overall survival times in 364 Asian GC patients from the Asian Cancer Research Group (ACRG) and The Cancer Genome Atlas (TCGA) databases was performed, and a novel prognostic index was established. To further explore regulatory prognosis mechanisms and therapeutic targets, a tumor immunogenomic landscape analysis, including stromal and immune subcomponents, cell types, panimmune gene sets, and immunomodulatory genes, was performed.ResultOur analysis allowed the creation of an optimal risk assessment model, the Asian-specific IRG-based prognostic index (ASIRGPI), which showed a high accuracy in predicting survival in Asian GC. We also developed an ASIRGPI-based nomogram to predict the 3- and 5-year overall survival (OS) of Asian GC patients. The impact of the ASIRGPI on the worse prognosis of Asian GC was possibly related to the stromal component remodeling. Specifically, TGFβ gene sets were significantly associated with the ASIRGPI and worse prognosis. Immunomodulatory gene analysis further revealed that TGFβ1 and EDNRB may be the novel potential therapeutic targets for Asian GC.ConclusionsAs a tumor microenvironment-relevant gene set-based prognostic signature, the ASIRGPI model provides an effective approach for evaluating the prognosis of Asian GC and may even prolong OS by enabling the selection of individualized therapy with the novel targets.
format	article
author	Chenchen Mao Liangliang Ma Yingpeng Huang Xinxin Yang He Huang Wentao Cai Andriamifehimanjaka Sitrakiniaina Ruihong Gu Xiangyang Xue Xian Shen
author_facet	Chenchen Mao Liangliang Ma Yingpeng Huang Xinxin Yang He Huang Wentao Cai Andriamifehimanjaka Sitrakiniaina Ruihong Gu Xiangyang Xue Xian Shen
author_sort	Chenchen Mao
title	Immunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer
title_short	Immunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer
title_full	Immunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer
title_fullStr	Immunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer
title_full_unstemmed	Immunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer
title_sort	immunogenomic landscape and immune-related gene-based prognostic signature in asian gastric cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/64b2dd225a2f4a4388173d0f609f8ed8
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Immunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer

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