RNA modification pattern-based subtypes reveal heterogenous clinical outcomes and tumor immunity of clear cell renal cell carcinoma

Abstract

RNA methylation plays a key role across biological processes, which could be utilized as new weapons for cancer management. However, the implication of RNA methylation regulators in cancers, especially in clear cell renal cell cancer (ccRCC), remains largely unknown. We investigated the multiomics profile of RNA methylation regulators at the pan-cancer level. We found most RNA methylation regulators were dysregulated in cancers, which might be explained by genomic mutation and copy number variation. A novel subtype of ccRCC, RNA modification cancer subtype 2 (RMCS2), was identified and verified among different ccRCC cohorts. RMCS2 led to a shortened overall survival and had an activated state of PI3K-AKT-mTOR, KRAS, and retinoic acid metabolism signals, which resulted in an immune exhausted phenotype. In summary, our findings demonstrated that the aberrance of RNA methylation regulators was a common biological phenomenon pan-cancer. Dysregulated RNA methylation patterns could reshape tumor immunity thus impacting patients' prognosis and therapeutic response, and could function as a promising tool for ccRCC patients.