Cross-talk of RNA modification "writers" describes tumor stemness and microenvironment and guides personalized immunotherapy for gastric cancer

Background: RNA modifications, TME, and cancer stemness play significant roles in tumor development and immunotherapy. The study investigated cross-talk and RNA modification roles in the TME, cancer stemness, and immunotherapy of gastric cancer (GC). Methods: We applied an unsupervised clustering method to distinguish RNA modification patterns in GC. GSVA and ssGSEA algorithms were applied. The WM_Score model was constructed for evaluating the RNA modification-related subtypes. Also, we conducted an association analysis between the WM_Score and biological and clinical features in GC and explored the WM_Score model’s predictive value in immunotherapy. Results: We identified four RNA modification patterns with diverse survival and TME features. One pattern consistent with the immune-inflamed tumor phenotype showed a better prognosis. Patients in WM_Score high group were related to adverse clinical outcomes, immune suppression, stromal activation, and enhanced cancer stemness, while WM_Score low group showed opposite results. The WM_Score was correlated with genetic, epigenetic alterations, and post-transcriptional modifications in GC. Low WM_Score was related to enhanced efficacy of anti-PD-1/L1 immunotherapy. Conclusions: We revealed the cross-talk of four RNA modification types and their functions in GC, providing a scoring system for GC prognosis and personalized immunotherapy predictions.