m6A RNA methylation regulators contribute to malignant progression and have clinical prognostic impact in gliomas

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.