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

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.

Identification and Comprehensive Prognostic Analysis of a Novel Chemokine-Related lncRNA Signature and Immune Landscape in Gastric Cancer

“…All these studies aim to find a reliable signature for predicting prognosis, immune cells infiltration and immune response of GC. Dai identified that low-risk patients in their risk model have a higher tumor mutation burden (TMB) score and immunotherapy score than that in high-risk group (Dai et al, 2021), which is similar to our results. Ma established an immune-related lncRNA signature which has a preferable performance in prognosis and immune cell infiltration prediction.…”

“…Some noncoding RNAs such as circRNAs and lncRNAs could also act as diagnostic biomarkers or prognostic factors in GC (Yang et al, 2016;Shan et al, 2019). A recent study identified an immune-related signature composed of MAGED1, ACKR3, FZD2, and CTLA4 could be used to predict the prognosis of GC patients (Dai et al, 2021). These molecular analyses have increased our knowledge of GC biology and might provide new insights on GC therapy strategies.…”

Identification of the Immune Subtype of Hepatocellular Carcinoma for the Prediction of Disease-Free Survival Time and Prevention of Recurrence by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data

“…Among these three immune cell types, effector memory CD8 T cells were the only protective factor with a risk coefficient less than zero. Effector memory CD8 T cells have been reported to play a role in IL-15 signaling-related antitumor activity of PD-1 inhibitors, as well as prognosis prediction of gastric cancer, lung cancer and ovarian cancer ( 45 – 48 ). However, its role in prognosis prediction and cancer recurrence remains largely unknown.…”

A Risk Signature Established From Three Coagulation-fibrinolysis Genes Predicts Prognosis in Digestive System Pancancer

“…MSI refers to the phenomenon of the appearance of new microsatellite alleles in tumors due to changes in microsatellite length caused by the insertion or deletion of repeat units compared with normal tissues. Recently, in a study on the immune-related signature of gastric cancer, TMB was found to be higher in the low-risk group [31].It has been demonstrated that CNV, TMB, and MSI are associated with poor prognosis of cancer [32,33]. In breast cancer, Xin Jin et al performed a comprehensive analysis of CNV, MSI, and TMB data from TCGA, which resulted in two genetic variation associated.…”