State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, 510632, People's Republic of China.
J Hematol Oncol. 2020 Mar 18;13(1):22. doi: 10.1186/s13045-020-00854-w.
Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (mA) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between mA and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between mA and 5mC regulators across ~ 11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between mA and 5mC methylation at the multiomic level. Then, we further established mA/5mC epigenetic module eigengenes by combining hub mA/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.
RNA 和 DNA 的甲基化，特别是分别以 N6-甲基腺苷 (mA) 和 5-甲基胞嘧啶 (5mC) 的形式，在多种生物过程中发挥着关键作用。目前，人们对 mA 和 5mC 调控因子之间的相互作用知之甚少。因此，我们通过对代表 33 种癌症类型的约 11000 个样本进行泛癌症基因组分析，系统地描绘了 mA 和 5mC 调控因子之间的分子相关性。我们首次在多组学水平上鉴定了 mA 和 5mC 甲基化之间的相互作用。然后，我们通过结合枢纽 mA/5mC 调控因子，进一步建立了 mA/5mC 表观遗传模块特征基因，并提供了全面的表观遗传状态信息。该模型反映了肿瘤免疫基质微环境的状态，并能够预测大多数癌症类型的患者生存情况。我们的研究结果为人类癌症中的表观遗传调控奠定了坚实的基础，并为相关治疗靶点开辟了新的道路。
