Molecular features, biological behaviors and clinical implications of m⁵C RNA methylation modification regulators in...

Epitranscriptome studies have shown that critical RNA modifications drive tumorigenicity; however, the role of 5-methylcytosine (m⁵C) RNA methylation remains poorly understood. We extracted 17 m⁵C regulators and clustered distinct m⁵C 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 m⁵C RNA methylation was commonly upregulated in gastrointestinal cancer and related to prognosis. Clusters were identified for m⁵C patterns, with distinct immune infiltrations and functional pathways. The risk scores of m⁵C regulators were independent risk factors. Differentially expressed mRNAs (DEmRNAs) in m⁵C clusters were involved in cancer-related pathways. The methylation-based m⁵Cscore showed a significant effect on the prognosis. Patients with a lower m⁵Cscore 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 m⁵Cscore in pancreatic cancer. We uncovered dysregulations of m⁵C-related regulators in gastrointestinal cancer and their associations with overall survival. Some immune cells were differently infiltrated in distinct m⁵C modification patterns, indicating their potential impacts on gastrointestinal cancer cell-immune. Moreover, an m⁵Cscore, derived from DEmRNAs in specific clusters, can serve as a classifier for immunotherapy.