Genetic Alterations and Transcriptional Expression of m 6A RNA Methylation Regulators Drive a Malignant Phenotype and Have Clinical Prognostic Impact in Hepatocellular Carcinoma

Background: N6-methyladenosine (m6A) RNA methylation, associated with cancer initiation and progression, is dynamically regulated by the m6A RNA regulators. However, its role in liver carcinogenesis is poorly understood. Methods: 371 hepatocellular carcinoma (HCC) patients from the Cancer Genome Atlas database with sequencing and copy number variations/mutations data were included. Survival analysis was performed using log-rank tests and Cox regression model. We explored the associations between m6A regulators and the mutated occurred genes in HCC. Gene set enrichment analysis was performed to investigate the functions correlated with different subgroups of HCC. Finally, we used machine-learning model to selected regulators for further functional analysis and development of a risk signature (m6Ascore). ROC analysis were performed to evaluate the prognostic performance. Findings: We demonstrated that eleven m6A RNA regulators are significantly differentially expressed among 371 HCC patients stratified by clinicopathological features (P