Significance of a Tumor Mutation Burden Gene Signature with Prognosis and Immune Feature of Gastric Cancer Patients

Abstract

Gastric cancer (GC) is a common digestive tumor which ranks the fourth most common malignancy worldwide. Immunotherapy is a promising treatment for GC, especially for advanced gastric cancer (AGC). However, in clinical practice, not all patients are sensitive to immunotherapy. Recent studies showed that tumor mutation burden (TMB) is closely correlated with the response of immunotherapy. The current study identified a TMB-related genes’ signature to predict the prognosis and immune feature of GC patients. Firstly, we acquired the TMB data and expression data from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) GEO databases. Then, we extracted TMB-related genes from the expression data of TCGA and two GEO cohorts. By using univariate Cox analysis, we identified that the 429 genes were correlated to GC patients’ overall survival. Subsequently, an immune prognostic signature was constructed by using the least absolute shrinkage and selection operator analysis (LASSO) and multivariate Cox regression analysis. The signature could be utilized to predict the prognosis of GC patients. In addition, the signature showed a closed correlation with immune feature of GC patients. In conclusion, our risk signature could offer hints for the prognosis of GC patients and might provide insights to formulate new immunotherapy strategies for GC patients.

Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer

“…Although most of studies demonstrated that TMB-H GC patients could benefit from a good prognosis [12] , [13] , [14] , [15] , [16] , [17] , [18] (Table S1), there are still some studies in Chinese GC cohorts suggested TMB-H GC patients might suffer from poor prognosis [19] , [20] , [21] (Table S1). It was also reported that the TMB related genes’ signature has a predictive function in GC patients [13] , [22] , [23] . The predictive significance of TMB deserves further exploration in GC, especially in Chinese GC patients.…”