Xu Nizhen, Chen Jian, He Gaofei, Gao Li, Zhang Deguang
Department of Head and Neck surgery, Institute of Micro-Invasive Surgery of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou 310016, P.R. China.
J Cancer. 2020 Jul 6;11(17):5187-5197. doi: 10.7150/jca.41193. eCollection 2020.
N6-methyladenosine (m6A) is the most prevalent modification of RNA in mammals. m6A RNA methylation levels are dynamically regulated by m6A RNA methylation regulators. While increasing evidence has suggested that m6A RNA methylation is vital in the initiation and progression of human carcinoma, little is known about the expression and effect of m6A RNA methylation regulators in differentiated thyroid carcinoma (DTC). Herein, we demonstrate that most of the thirteen main m6A RNA methylation regulators are differentially expressed in DTC tissues and normal thyroid tissues. Based on consensus clustering of m6A RNA methylation regulators, DTC cases were divided into two subgroups (TC1 and TC2). Compared with the TC1 subgroup, the TC2 subgroup was associated with a poorer prognosis, older age, higher T grade, higher N grade and higher TNM stage. The results indicated that alteration of m6A RNA methylation regulators was closely related to DTC. We further established a risk signature of four m6A RNA methylation regulators that could evaluate prognosis and clinicopathological features in DTC. Finally, the results of the TCGA analysis were verified by other cohorts from Gene Expression Omnibus (GEO) database. In conclusion, m6A RNA methylation regulators play a crucial part in the progression of DTC and are potentially useful for evaluating the prognosis and providing potential novel insights into treatment strategies.
N6-甲基腺苷（m6A）是哺乳动物中最普遍的RNA修饰。m6A RNA甲基化水平由m6A RNA甲基化调节因子动态调控。虽然越来越多的证据表明m6A RNA甲基化在人类癌症的发生和发展中至关重要，但关于m6A RNA甲基化调节因子在分化型甲状腺癌（DTC）中的表达及作用却知之甚少。在此，我们证明了13种主要的m6A RNA甲基化调节因子中的大多数在DTC组织和正常甲状腺组织中存在差异表达。基于m6A RNA甲基化调节因子的一致性聚类，DTC病例被分为两个亚组（TC1和TC2）。与TC1亚组相比，TC2亚组与较差的预后、年龄较大、较高的T分级、较高的N分级和较高的TNM分期相关。结果表明，m6A RNA甲基化调节因子的改变与DTC密切相关。我们进一步建立了一个由4种m6A RNA甲基化调节因子组成的风险特征模型，该模型可评估DTC的预后和临床病理特征。最后，来自基因表达综合数据库（GEO）的其他队列验证了TCGA分析的结果。总之，m6A RNA甲基化调节因子在DTC的进展中起关键作用，并且在评估预后和为治疗策略提供潜在的新见解方面可能具有重要价值。
