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

Chenchen Mao; Liangliang Ma; Yingpeng Huang; Xinxin Yang; He Huang; Wentao Cai; Andriamifehimanjaka Sitrakiniaina; Ruihong Gu; Xiangyang Xue; Xian Shen

doi:10.3389/fonc.2021.750768

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

Front Oncol. 2021 Nov 5:11:750768. doi: 10.3389/fonc.2021.750768. eCollection 2021.

Authors

Affiliations

¹ Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Vascular Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of General Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
⁴ Department of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou, China.

Abstract

Background: Asians 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.

Methods: To 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.

Result: Our 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.

Conclusions: As 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.

Keywords: Asian cancer; gastric cancer; immunomodulatory gene; immunotherapy; prognostic gene signature.