M6A-Related Bioinformatics Analysis Reveals a New Prognostic Risk Signature in Cutaneous Malignant Melanoma

Cutaneous malignant melanoma (CMM) is the most deadly skin cancer worldwide. Despite advances in the treatments of CMM, its incidence and mortality rates are still increasing. N6-methyladenosine (m6A) is the most common form of RNA modification and has attracted increasing interest in cancer initiation and progression. However, the role of m6A regulators in CMM and their correlation with prognosis remain elusive. Here, we demonstrated that by applying consensus clustering, all CMM patient cases can be divided into two clusters based on overall expression levels of 25 m6A genes. We systematically analyzed the prognostic value of the 25 m6A RNA methylation regulators in CMM and found that ELAVL1, ABCF1, and IGF2BP1 yield the highest scores for predicting the prognosis of CMM. Accordingly, we derived a risk signature consisting of three selected m6A genes as an independent prognostic marker for CMM and validated our findings with data derived from a different CMM cohort. Next, we determined that CNVs in m6A genes had a significant negative impact on patient survival. The mRNA expression levels of m6A genes were correlated with CNV mutation. Moreover, in the selected three risk signature m6A regulators, GSEA analysis showed that they were closely correlated with inflammation and immune pathways. TME analysis proved that m6A gene expressions were negatively correlated with immune cell infiltration. In conclusion, m6A regulators are vital participants in CMM pathology; and ELAVL1, ABCF1, and IGF2BP1 mRNA levels are valuable factors for prognosis prediction and treatment strategy development.