Identification of cross-talk between m6A and 5mC regulators associated with onco-immunogenic features and prognosis across 33 cancer types
Yutong Chen, Jiayi Shen, Dong‐Ping Chen, Chen‐Fei Wu, Rui Guo, Panpan Zhang, Jia‐Wei Lv, Wenfei Li, Zixian Wang, Yu‐Pei Chen
Abstract
Abstract Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m 6 A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m 6 A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m 6 A and 5mC regulators across ~ 11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m 6 A and 5mC methylation at the multiomic level. Then, we further established m 6 A/5mC epigenetic module eigengenes by combining hub m 6 A/5mC regulators and informed a comprehensive epigenetic state. The model reflected status of the tumor-immune-stromal microenvironment and was able to predict patient survival in the majority of cancer types. Our results lay a solid foundation for epigenetic regulation in human cancer and pave a new road for related therapeutic targets.