Identification and Verification of Molecular Subtypes with Enhanced Immune Infiltration Based on m6A Regulators in Cutaneous Melanoma

Abstract

Background. As the most aggressive type of skin cancer, cutaneous melanoma (CM) is experiencing a rapidly rising mortality in recent years. Exploring potential prognostic biomarkers or mechanisms of disease progression therefore has a great significance for CM. The purpose of this study was to identify genetic markers and prognostic performance of N6-methyladenosine (m6A) regulators in CM. Method. Gene expression profiles, copy number variation (CNV), and single nucleotide polymorphism (SNP) data of patients were obtained from The Cancer Genome Atlas (TCGA) database. Results. Genomic variation and association analysis of gene expressions revealed a high degree of genomic variation in the presence of m6A-regulated genes. m6A patients with high-frequency genomic variants in the regulatory gene tended to develop a worse prognosis ( $p<0.01$ ). Unsupervised cluster analysis of the expression profiles of m6A-regulated genes identified three clinically distinct molecular subtypes, including degradation-enhanced subgroup and immune-enhanced subgroup, with significant prognostic differences ( $p=0.046$ ). A novel prognostic signature, which was established according to m6A-related characteristic genes identified through genome-wide expression spectrum, could effectively identify samples with poor prognosis and enhanced immune infiltration, and the effectiveness was also verified in the dataset of the chip. Conclusion. We identified genetic changes in the m6A regulatory gene in CM and related survival outcomes. The findings of this study provide new insights into the epigenetic understanding of m6A in CM.