Identification of a Gene Prognostic Model of Gastric Cancer Based on Analysis of Tumor Mutation Burden

Abstract

Introduction: Gastric cancer is one of the most common cancers. Although some progress has been made in the treatment of gastric cancer with the improvement of surgical methods and the application of immunotherapy, the prognosis of gastric cancer patients is still unsatisfactory. In recent years, there has been increasing evidence that tumor mutational load (TMB) is strongly associated with survival outcomes and response to immunotherapy. Given the variable response of patients to immunotherapy, it is important to investigate clinical significance of TMB and explore appropriate biomarkers of prognosis in patients with gastric cancer (GC).Material and Methods: All data of patients with gastric cancer were obtained from the database of The Cancer Genome Atlas (TCGA). Samples were divided into two groups based on median TMB. Differently expressed genes (DEGs) between the high- and low-TMB groups were identified and further analyzed. We identified TMB-related genes using Lasso, univariate and multivariate Cox regression analysis and validated the survival result of 11 hub genes using Kaplan-Meier Plotter. In addition, “CIBERSORT” package was utilized to estimate the immune infiltration.Results: Single nucleotide polymorphism (SNP), C > T transition were the most common variant type and single nucleotide variant (SNV), respectively. Patients in the high-TMB group had better survival outcomes than those in the low-TMB group. Besides, eleven TMB-related DEGs were utilized to construct a prognostic model that could be an independent risk factor to predict the prognosis of patients with GC. What’s more, the infiltration levels of CD4+ memory-activated T cells, M0 and M1 macrophages were significantly increased in the high-TMB group compared with the low-TMB group.Conclusions: Herein, we found that patients with high TMB had better survival outcomes in GC. In addition, higher TMB might promote immune infiltration, which could provide new ideas for immunotherapy.

Construction and Validation of a Novel Pyroptosis-Related Four-lncRNA Prognostic Signature Related to Gastric Cancer and Immune Infiltration

“…Moreover, the high- and low-risk groups exhibited different CNV, TMB, and immune cell infiltration signatures, demonstrating that PRL may play a key modifying role in the regulation of TME and tumor immunity in STAD. In particular, the low-risk group had a higher TMB than the high-risk group, while the low-risk group with a high TMB presented a better prognosis in the STAD cohort, which is consistent with the results of other studies ( 46 , 47 ). Based on the tumor immune editing hypothesis ( 48 ), accompanied by the progression of tumor cells in immunocompetent hosts, fewer immunogenic cancer cells are targeted to evade the antitumor immune response.…”

Integrated Analysis of Multi-Omics Alteration, Immune Profile, and Pharmacological Landscape of Pyroptosis-Derived lncRNA Pairs in Gastric Cancer

“…Subsequently, we found that genomic differences in patients with subgroups were abundant. As is well known, the TMB is associated with tumor immunity, and low TMB is a poor prognostic factor in GC (Roh et al, 2017;Ma et al, 2021). This is consistent with the results of the correlation analysis in our study, where patients in the high-risk group had lower TMB.…”

The Pan-Cancer Crosstalk Between the EFNA Family and Tumor Microenvironment for Prognosis and Immunotherapy of Gastric Cancer

“…In terms of prognosis, the MSI subtype was superior to the microsatellite stable subtype, and this advantage was more significant in the Chinese population ( Cai et al, 2020 ). Ma et al established a prognostic marker of gastric cancer based on 11 TMB differential genes and found that high TMB may promote immune infiltrate, and patients with high TMB showed a better prognosis ( Ma et al, 2021 ). Baseline tumor burden factors, such as the sum of maximum tumor size and target lesion size, can be used in combination with TMB to evaluate the efficacy of immune checkpoint inhibitors in advanced gastric cancer ( Wei X.-L. et al, 2021 ).…”

“…In terms of prognosis, the MSI subtype was superior to the microsatellite stable subtype, and this advantage was more significant in the Chinese population (Cai et al, 2020). Ma et al established a prognostic marker of gastric cancer based on 11 TMB differential genes and found that high TMB may promote immune infiltrate, and patients with high TMB showed a better prognosis (Ma et al, 2021).…”