Omics-based evaluation of m6A modification patterns in uveal melanoma and their prognostic implications

• This study is the first to investigate m6A RNA methylation patterns at the transcriptomic level in uveal melanoma (UM). • We identified distinct m6A modification patterns and developed a robust m6A scoring system. • Higher m6A scores were significantly associated with better prognosis and improved patient outcomes. • The m6A score was linked to immune cell infiltration and tumor mutational burden (TMB), suggesting its role in UM pathogenesis. • Our findings highlight the potential of m6A modification as a prognostic biomarker and a target for novel therapeutic strategies in UM. Epigenetic reprogramming plays a crucial role in the progression of uveal melanoma (UM). RNA methylation constitutes more than 60% of all RNA modifications, with N6-methyladenosine (m6A) being the most prevalent RNA modification in higher organisms. This study aimed to investigate the construction of the m6A regulatory factor modification model and its assessment of UM clinical prognosis. The expression levels of 23 m6A regulators in The Cancer Genome Atlas (TCGA) were analyzed, and the survival rate was assessed based on TCGA clinicopathological data. Consistent cluster analysis was performed to evaluate different m6A scores in tumor mutation burden (TMB) and to predict the correlation between m6A scores and UM prognosis. Various expression patterns of m6A regulators were observed in UM tumors, and multiple m6A genes were found to be correlated with prognosis. Through consistent cluster analysis, three distinct m6A modification patterns were identified. The overlapping differentially expressed genes (DEGs) among the three m6A clusters were screened, leading to the establishment of three different subgroups. Among these subgroups, cluster B exhibited the most favorable prognosis. Based on the m6A score derived from DEGs, UM patients could be categorized into a high-scoring subgroup and a low-scoring subgroup. Importantly, patients with higher m6A scores demonstrated prolonged survival and improved clinical characteristics. Furthermore, the study established an association between the m6A score and TMB, suggesting that the m6A score may serve as a potential prognostic predictor for UM patients. We conducted a screening of DEGs from the m6A cluster and categorized them into three distinct clusters for analysis of m6A scores. Subsequently, we developed a highly predictive model with prognostic value. This study will contribute to our understanding of the overall impact of m6A modification patterns on the progression of UM.