N7-methylguanosine-based signature for tumor subtyping and prognosis and immunotherapy prediction of stomach cancer

Background Gastric cancer is an aggressive disease with complex tumor heterogeneity, influenced by genomic, transcriptomic, and translational processes. N7-methylguanylate (m7G) modification is a potential factor in tumor heterogeneity, but its role in gastric cancer remains unclear. Methods We conducted cluster analysis on m7G-related genes in the TCGA-STAD dataset to identify gene patterns. Using LASSO regression, we identified genes that were differentially expressed in relation to m7G. A nomogram was developed to predict patient prognosis based on these genes. To further explore the molecular mechanisms, we performed survival analysis, functional enrichment analysis, and gene silencing experiments. Additionally, we examined tumor mutations, immune cell infiltration, and immune-related genes to evaluate immune responses and drug sensitivity. Results Clustering analysis identified two main gene groups linked to m7G modification. Survival analysis showed that high-risk patients, based on the selected genes, had poorer outcomes. Functional enrichment revealed that m7G modification influences tumor heterogeneity and the tumor microenvironment (TME), impacting prognosis. Silencing RASGRF2, the most significantly impacted gene, inhibited survival, proliferation, invasion, and migration of gastric cancer cells (AGS and HGC-27). Correlation analysis of immune responses and mutation patterns suggested that m7G modification affects the effectiveness of immunotherapy and drug sensitivity. Conclusions m7G modification plays a critical role in gastric cancer, influencing tumor heterogeneity and prognosis. The predictive nomogram provides a robust tool for forecasting patient survival, and targeting m7G modification could offer new therapeutic opportunities.