Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m6A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m6A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m6A and 5mC regulators across ~ 11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m6A and 5mC methylation at the multiomic level. Then, we further established m6A/5mC epigenetic module eigengenes by combining hub m6A/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.

中文翻译：

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鉴定与 33 种癌症类型的致癌免疫原性特征和预后相关的 m6A 和 5mC 调节因子之间的串扰。

RNA 和 DNA 的甲基化，特别是分别以 N6-甲基腺苷 (m6A) 和 5-甲基胞嘧啶 (5mC) 的形式，在不同的生物过程中起着至关重要的作用。目前，对 m6A 和 5mC 稳压器之间的串扰缺乏了解。因此，我们通过描述代表 33 种癌症类型的约 11,000 名受试者的 m6A 和 5mC 调节因子之间的分子相关性，系统地进行了泛癌基因组分析。我们首次在多组学水平上确定了 m6A 和 5mC 甲基化之间的串扰。然后，我们通过结合中枢 m6A/5mC 调节因子进一步建立了 m6A/5mC 表观遗传模块特征基因，并告知全面的表观遗传状态。该模型反映了肿瘤-免疫-基质微环境的状态，并且能够预测大多数癌症类型的患者存活率。