RNA m⁵C regulator-mediated modification patterns and the cross-talk between tumor microenvironment infiltration in...

The effect of immunotherapy strategy has been affirmed in the treatment of various tumors. Nevertheless, the latent role of RNA 5-methylcytosine (m⁵C) modification in gastric cancer (GC) tumor microenvironment (TME) cell infiltration is still unclear. We systematically explore the m⁵C modification patterns of 2,122 GC patients from GEO and TCGA databases by 16 m⁵C regulators and related these patterns to TME characteristics. LASSO Cox regression was employed to construct the m⁵Cscore based on the expression of regulators and DEGs, which was used to evaluate the prognosis. All the GC patients were divided into three m⁵C modification clusters with distinct gene expression characteristics and TME patterns. GSVA, ssGSEA, and TME cell infiltration analysis showed that m⁵C clusters A, B, and C were classified as immune-desert, immune-inflamed, and immune-excluded phenotype, respectively. The m⁵Cscore 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 m⁵Cscore were characterized by the activation of immunity and experienced significantly longer PFS and OS. Our study demonstrated the non-negligible role of m⁵C modification in the development of TME complexity and inhomogeneity. Assessing the m⁵C modification pattern for individual GC patients will help recognize the infiltration characterization and guide more effective immunotherapy treatment.