A comparative transcriptomic analysis at single-cell resolution reveals acral melanoma features distinct from cutaneous melanoma.

Objective: Acral melanoma (AM), a unique subtype prevalent in China, develops on the palms, soles, and nail beds. Despite its distinct clinical and pathological features compared to cutaneous melanoma (CM), the molecular basis underlying these differences remains poorly understood. This study aims to perform a comprehensive comparative transcriptomic analysis of AM and CM at the single-cell level to uncover key molecular distinctions.

Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data from 39 AM patients and 18 CM cases. Single-cell transcriptomic profiling was used to compare tumor cell subpopulations and microenvironmental differences. Bioinformatics tools were employed for cell clustering, differential gene expression analysis, cell-cell communication network inferences, and survival analysis.

Results: AM exhibited a significantly higher proportion of MPZ ⁺ melanoma cells, a subpopulation with Schwann cell-like properties associated with poor prognosis. These MPZ ⁺ melanoma cells established extensive communication networks with AM-specific immune and stromal components, prompting an immunosuppressive microenvironment and enhancing angiogenic potential. Survival analysis further indicated that the presence of MPZ ⁺ melanoma cells is closely linked to worse clinical outcomes in AM patients.

Conclusions: This study provides novel insights into the molecular distinctions between AM and CM, highlighting the critical role of MPZ ⁺ melanoma cells in AM progression. These findings enhance our understanding of AM pathophysiology and may contribute to the development of more targeted therapeutic strategies.