Integrating single-cell and bulk RNA sequencing to identify disulfidptosis-related gene signature, immune landscape, and immunotherapy targets in cutaneous melanoma.

Disulfidptosis as a novel non-apoptotic cell death mode has exhibited considerable potential for clinical application in anti-tumor treatments. However, the precise molecular mechanism underlying disulfidptosis in cutaneous melanoma and its potential clinical value remain poorly characterized. The present study validated the sensitivity of melanoma cells to glucose deprivation-induced disulfidptosis in vitro. Subsequently, single-cell sequencing data from four cutaneous melanoma patients were analyzed to identify disulfidptosis-associated differentially expressed genes (DEGs) in melanoma. Next, 472 melanoma patients were divise into two subclusters based on DEG expression, and the genomic features and immune landscape of these clusters were evaluated. Ultimately, pivotal DEGs were screened, and their expression in clinical specimens was further validated. The results showed that the A-375 melanoma cell line was sensitive to glucose deprivation-induced disulfidptosis mediated by solute carrier family 7, membrane 11 (SLC7A11). Single-cell sequencing analysis revealed that disulfidptosis may be more likely to occur during the early and terminal differentiation stages. Furthermore, a comparison of melanoma cell clusters with high and low disulfidptosis scores identified 75 DEGs. Notably, the two subtypes defined by these DEGs exhibited significantly distinct prognoses, biological characteristics, immunotherapy response, and tumor mutation burdens, which is beneficial for clinical decision-making. Additionally, three hub genes were identified, including beta-2-microglobulin (B2M), human leukocyte antigen-A (HLA-A), and HLAB, and their expression was decreased in melanoma lesions compared with nevus. In conclusion, this study elucidated the gene expression signature of disulfidptosis in melanoma and its potential implications for immune treatment and prognosis. Moreover, B2M, HLA-A, and HLA-B emerge as promising therapeutic targets related to disulfidptosis in cutaneous melanoma.