Single-cell analysis unveils cell subtypes of acral melanoma cells at the early and late differentiation stages

Background: Melanoma, a malignant neoplasm originating from melanocytes, is a form of skin cancer with rapidly increasing global incidence, often exacerbated by UV radiation[1]. Particularly, acral melanoma, characterized by its swift metastasis and poor prognosis, underscores the significance of further research into its heterogeneity. Single-cell sequencing has been widely utilized in the study of tumor heterogeneity; however, research related to melanoma remains to be further refined.

Materials and methods: We employed single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to delve into the melanoma cells from six samples of melanoma patients. This approach enabled the identification of critical melanoma cell subpopulations and their roles in melanoma progression. Subsequently, we examined the interactions among these subpopulations and analyzed their interactions with other cell types.

Results: Our analysis identified C3 ID2+ melanoma cells as an early-stage subpopulation and C4 PCLAF+ cells as a late-stage subpopulation in melanoma evolution. Through our analysis, we identified C4 PCLAF+ Melanoma cells as a significant subpopulation in acral melanoma (AM), playing a pivotal role in the differentiation and development of AM. Further analysis of transcription factors, enriched pathways, cell stemness, and cell trajectories highlighted the significant role of C4 PCLAF+ melanoma cells in acral melanoma (AM) proliferation.

Conclusion: This study identifies new factors influencing melanoma progression, providing a foundation for subsequent research.