Revealing tumor microenvironment communication through m6A single-cell analysis and elucidating immunotherapeutic potentials for cutaneous melanoma (CM)
Background The methylation of N6-methyladenosine (m6A) RNA plays a crucial role in the genetic regulation of various cancers. While m6A modifications have been extensively studied in the tumor microenvironment (TME) of several malignancies, their role in cutaneous melanoma (CM) remains unexplored. Methods Using Non-negative matrix factorization (NMF) analysis on single-cell RNA-seq data (GSE215121) from three CM samples obtained from public databases, 26 m6A RNA methylation regulators were utilized to determine TME subclusters, their expression, and function. Results Six distinct TME cell types were identified and NMF clustering further revealed unique m6A-based subpopulations of cancer-associated fibroblasts and T cells. The prognostic model demonstrated strong predictive capabilities, particularly for fibroblast and T cell m6A clusters, and highlighted COL3A1 as a critical regulator of melanoma-fibroblast interactions. Conclusion Highlighting the COL3A1 gene as a critical link and potential therapeutic target in melanoma could offer new avenues for targeted therapies and improve prognostic assessments in cutaneous melanoma.