Gene Signatures and Prognostic Values of m6A Regulators in Hepatocellular Carcinoma.

N6-methyladenosine (m6A) is the most abundant mRNA modification in mammals and has been implicated in various biological processes. However, its role in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we investigated the alterations of 19 main m6A regulatory genes in HCC and their association with clinicopathological features, including survival. The mutation, copy number variation (CNV) and clinical data of HCC patients were retrieved from The Cancer Genome Atlas (TCGA) database. We found that the m6A regulators had high frequent alterations in HCC. The alterations of m6A regulators were significantly associated with clinicopathological features as well as TP53 alteration. Patients with any mutation of the m6A regulatory genes had worse overall survival (OS) and disease free survival (DFS). Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of HCC patients. Moreover, deletion of METTL16 was an independent risk factor for DFS. Low METT16 expression was association with activation of multiple metabolic pathways in HCC. Finally, by RT-PCR, we confirmed that METTL16 was downregulated in HCC, and that lower METTL16 expression was associated with poor OS. In conclusion, we reported a significant association between alterations of m6A regulators and clinicopathological features, and highlighted the importance of METTL16 among the 19 m6A regulators in HCC pathogenesis. These findings will provide new insights into the role of m6A modification in HCC.