Molecular features, biological behaviors and clinical implications of m 5 C RNA methylation modification regulators in gastrointestinal cancers.

Epitranscriptome studies have shown that critical RNA modifications drive tumorigenicity; however, the role of 5-methylcytosine (m 5 C) RNA methylation remains poorly understood. We extracted 17 m 5 C regulators and clustered distinct m 5 C modification patterns by consensus clustering analysis. Gene set variation and single-sample gene set enrichment analysis were applied to quantify functional analysis and immune infiltration. The least absolute shrinkage and selection operator was employed to develop a prognostic risk score. Kaplan-Meier with log-rank test was used for survival analysis. Differential expression analysis was performed with the "limma" R package. Wilcoxon signed ranked test or Kruskal-Wallis test was used to compare groups. We observed that m 5 C RNA methylation was commonly upregulated in gastrointestinal cancer and related to prognosis. Clusters were identified for m 5 C patterns, with distinct immune infiltrations and functional pathways. The risk scores of m 5 C regulators were independent risk factors. Differentially expressed mRNAs (DEmRNAs) in m 5 C clusters were involved in cancer-related pathways. The methylation-based m 5 Cscore showed a significant effect on the prognosis. Patients with a lower m 5 Cscore exhibited more therapeutic efficiency on anti-CTLA4 therapy in liver cancer, while the combination of anti-CTLA4 therapy and pd1 was more efficient for patients with a lower m 5 Cscore in pancreatic cancer. We uncovered dysregulations of m 5 C-related regulators in gastrointestinal cancer and their associations with overall survival. Some immune cells were differently infiltrated in distinct m 5 C modification patterns, indicating their potential impacts on gastrointestinal cancer cell-immune. Moreover, an m 5 Cscore, derived from DEmRNAs in specific clusters, can serve as a classifier for immunotherapy.