Identification of an Immune-Related Signature Predicting Survival Risk and Immune Microenvironment in Gastric Cancer

Shuang Dai; Tao Liu; Xiao-Qin Liu; Xiao-Ying Li; Ke Xu; Tao Ren; Feng Luo

doi:10.3389/fcell.2021.687473

Identification of an Immune-Related Signature Predicting Survival Risk and Immune Microenvironment in Gastric Cancer

Front Cell Dev Biol. 2021 Nov 2:9:687473. doi: 10.3389/fcell.2021.687473. eCollection 2021.

Authors

Shuang Dai¹, Tao Liu^{1

2}, Xiao-Qin Liu³, Xiao-Ying Li⁴, Ke Xu², Tao Ren², Feng Luo¹

Affiliations

¹ Department of Medical Oncology, Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
² Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu, China.
³ Department of Oncology, Jintang First People's Hospital, Chengdu, China.
⁴ Department of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Background: Tumor immune microenvironment plays a vital role in tumorigenesis and progression of gastric cancer (GC), but potent immune biomarkers for predicting the prognosis have not been identified yet. Methods: At first, RNA-sequencing and clinical data from The Cancer Genome Atlas (TCGA) were mined to identify an immune-risk signature using least absolute shrinkage and selection operator (LASSO) regression and multivariate stepwise Cox regression analyses. Furthermore, the risk score of each sample was calculated, and GC patients were divided into high-risk group and low-risk group based on their risk scores. Subsequently, the performance of this signature, including the correlation with overall survival (OS), clinical features, immune cell infiltration, and immune response, has been tested in GC data from TCGA database and Gene Expression Omnibus (GSE84437), respectively. Results: An immune signature composed of four genes (MAGED1, ACKR3, FZD2, and CTLA4) was constructed. The single sample gene set enrichment analysis (ssGSEA) indicated that activated CD4⁺/CD8⁺ T cell, activated dendritic cell, and effector memory CD8⁺ T cell prominently increased in the low-risk group, showing relatively high immune scores and low stromal scores. Further GSEA analysis indicated that TGF-β, Ras, and Rap1 pathways were activated in the high-risk group, while Th17/Th1/Th2 differentiation, T cell receptor and PD-1/PD-L1 checkpoint pathways were activated in the low-risk group. Low-risk patients presented higher tumor mutation burden (TMB) and expression of HLA-related genes. The immune-associated signature showed an excellent predictive ability for 2-, 3-, and 5-year OS in GC. Conclusion: The immune-related prognosis model contributes to predicting the prognosis of GC patients and providing valuable information about their response to immunotherapy using integrated bioinformatics methods.

Keywords: gastric cancer; immune infiltration; immune signature; survival; tumor mutation burden.