m6A RNA methylation regulators contribute to malignant progression and have clinical prognostic impact in gliomas
m6A RNA methylation regulators contribute to malignant progression and have clinical prognostic impact in gliomas
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m(6)A RNA 甲基化调节因子有助于恶性进展并对神经胶质瘤具有临床预后影响
DOI：
10.18632/aging.101829
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发表时间：
2019-02-28
期刊：
影响因子：
5.2
通讯作者：
Kang, Chun-Sheng
中科院分区：
文献类型：
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作者：
Chai, Rui-Chao;Wu, Fan;Kang, Chun-Sheng
N6-甲基腺苷（m（6）A）RNA甲基化与癌症的发生和进展相关，受m（6）A RNA甲基化调节因子（“写入者”、“擦除者”和“读取者”）的动态调节。在这里，我们证明了13个主要m（6）A RNA甲基化调节因子中的大多数在904个胶质瘤中的不同临床病理特征分层的胶质瘤中差异表达。我们通过对m（6）A RNA甲基化调节因子应用一致聚类法鉴定了两个胶质瘤亚组（RM 1/2）。与RM 1亚组相比，RM 2亚组与较差的预后、较高的WHO分级和较低的IDH突变频率相关。此外，上皮-间充质转化和通过NF-κ B的TNF α信号传导的标志在RM 2亚组中也显著富集。这一发现表明，m（6）A RNA甲基化调节因子与胶质瘤恶性程度密切相关。基于这一发现，我们使用7种m（6）A RNA甲基化调节因子推导出一种风险特征，它不仅是一种独立的预后标志物，而且还可以预测胶质瘤的临床病理学特征。此外，m（6）A调节因子与GBM的间充质亚型和TMZ敏感性相关。总之，m（6）A RNA甲基化调节因子是胶质瘤恶性进展的重要参与者，对预后分层和治疗策略的制定具有潜在的意义。
N6-methyladenosine (m(6)A) RNA methylation, associated with cancer initiation and progression, is dynamically regulated by the m(6)A RNA methylation regulators ("writers", "erasers" and "readers"). Here, we demonstrate that most of the thirteen main m(6)A RNA methylation regulators are differentially expressed among gliomas stratified by different clinicopathological features in 904 gliomas. We identified two subgroups of gliomas (RM1/2) by applying consensus clustering to m(6)A RNA methylation regulators. Compared with the RM1 subgroup, the RM2 subgroup correlates with a poorer prognosis, higher WHO grade, and lower frequency of IDH mutation. Moreover, the hallmarks of epithelial-mesenchymal transition and TNF alpha signaling via NF-kappa B are also significantly enriched in the RM2 subgroup. This finding indicates that m(6)A RNA methylation regulators are closely associated with glioma malignancy. Based on this finding, we derived a risk signature, using seven m(6)A RNA methylation regulators, that is not only an independent prognostic marker but can also predict the clinicopathological features of gliomas. Moreover, m(6)A regulators are associated with the mesenchymal subtype and TMZ sensitivity in GBM. In conclusion, m(6)A RNA methylation regulators are crucial participants in the malignant progression of gliomas and are potentially useful for prognostic stratification and treatment strategy development.