Prognosis and tumor immune microenvironment of patients with gastric cancer by a novel senescence-related signature.

Abstract

Background:Cellular senescence is a stable state of cell cycle arrest that plays a crucial role in the tumor microenvironment (TME) and cancer progression. Nevertheless, the accurate prognosis of gastric cancer (GC) is complicated to predict due to tumor heterogeneity. The work aimed to build a novel prognostic model in GC.Methods:LASSO and Cox regression analysis were constructed to develop a prognostic senescence-related signature. The Gene Expression Omnibus dataset was used for external validation of signature. Afterward, we performed correlation analysis for the risk score and the infiltrating abundance of immune cells, TME scores, drug response, tumor mutational burden (TMB), and immunotherapy efficacy.Results:Five senescence-related genes (AKR1B1, CTNNAL1, DUSP16, PLA2R1, and ZFP36) were screened to build a signature. The high-risk group had a shorter overall survival, cancer-specific survival, and progression-free survival when compared to the low-risk group. We further constructed a nomogram based on risk score and clinical traits, which can predict the prognosis of GC patients more accurately. Moreover, the risk score was evidently correlated with infiltration of immune cells, TME score, TMB, TIDE score, and chemotherapy sensitivity. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes pathway showed that the PI3K-Akt and Wnt signaling pathway were differentially enriched in the high-risk group.Conclusions:The senescence-related signature was an accurate tool to guide the prognosis and might promote the progress of personalized treatment.