RNA m(5)C regulator-mediated modification patterns and the cross-talk between tumor microenvironment infiltration in gastric cancer

The effect of immunotherapy strategy has been affirmed in the treatment of various tumors. Nevertheless, the latent role of RNA 5-methylcytosine (m(5)C) modification in gastric cancer (GC) tumor microenvironment (TME) cell infiltration is still unclear. We systematically explore the m(5)C modification patterns of 2,122 GC patients from GEO and TCGA databases by 16 m(5)C regulators and related these patterns to TME characteristics. LASSO Cox regression was employed to construct the m(5)Cscore based on the expression of regulators and DEGs, which was used to evaluate the prognosis. All the GC patients were divided into three m(5)C modification clusters with distinct gene expression characteristics and TME patterns. GSVA, ssGSEA, and TME cell infiltration analysis showed that m(5)C clusters A, B, and C were classified as immune-desert, immune-inflamed, and immune-excluded phenotype, respectively. The m(5)Cscore system based on the expression of eight genes could effectively predict the prognosis of individual GC patients, with AUC 0.766. Patients with a lower m(5)Cscore were characterized by the activation of immunity and experienced significantly longer PFS and OS. Our study demonstrated the non-negligible role of m(5)C modification in the development of TME complexity and inhomogeneity. Assessing the m(5)C modification pattern for individual GC patients will help recognize the infiltration characterization and guide more effective immunotherapy treatment.