The prognostic values of m6A RNA methylation regulators in uveal melanoma.

ABSTRACT

BACKGROUND: The aim of this study was to identify gene signatures and prognostic values of m6A methylation regulators in uveal melanoma (UM). METHODS: The RNA sequencing dataset and corresponding clinical information were downloaded from TCGA and GEO database. Based on the expression of m6A RNA methylation regulators, the patients were further clustered into different groups by applying the "ClassDiscovery" algorithm. Best survival analysis was performed to select prognostic m6A regulators and multivariate cox regression analysis was applied to constructed m6A regulators signature. The association between mutations and m6A regulators was assessed by Kruskal-Wallis tests and clinical characteristics were examined by using chi-square test. RESULTS: Totally, we identified two molecular subtypes of UM (C1/2) by applying consensus clustering to m6A RNA methylation regulators. In contrast to the C1 subtype, the C2 subtype associates with a better prognosis, has higher percentage of subtype 1 and lower percentage of Monosomy 3 which have been regarded as the well established prognostic markers for UM. The malignant hallmarks of mTORC1 signaling, oxidative phosphorylation, interferon-a response and apoptosis signaling are also significantly enriched in the C1 subtype. Moreover, a 3-m6A regulators signature was constructed by multivariate cox regression analysis method, which closely correlated with chromosome 3 status, subtype 1 of UM and can robustly predict patients' overall survival time. CONCLUSIONS: m6A RNA methylation regulators take a crucial role in the potential malignant progression and prognostic value of UM and might be regarded as a new promising biomarker for UM prognosis and treatment strategy development.