The prognostic implications of cuproptosis-related gene signature and the potential of PPIC as a promising biomarker in cutaneous melanoma

Abstract

Cutaneous melanoma is the most lethal of all skin tumors. Recently, cuproptosis, a novel form of cell death linked to oxidative phosphorylation, has emerged as an important factor. However, the precise role of cuproptosis in melanoma remains unclear. Our research explored the potential links between cuproptosis-related genes, prognosis, immune microenvironments, and melanoma treatments. Significantly, cuproptosis regulators showed remarkable differences between melanoma and normal tissues, establishing their relevance to melanoma. The newly developed cuproptosis-related gene signature (CGS) demonstrated a robust ability to predict overall survival (OS) in melanoma. We constructed a novel nomogram that combined clinical features with CGS to improve predictive accuracy. In addition, the study revealed correlations between CGS and immune cell populations, including CD8⁺T cells, Tfh cells, B cells, and myeloid-derived suppressor cells. Within the CGS, Peptidylprolyl isomerase C (PPIC) emerged as the most strongly associated with poor prognosis and drug resistance in melanoma. PPIC was identified as a promoter of melanoma progression, enhancing cell invasiveness while concurrently suppressing CD8⁺T cell activation. This comprehensive study not only elucidated the intricate connections between CGS, melanoma prognosis, immune microenvironment, and drug resistance but also provided compelling evidence supporting PPIC as a promising biomarker for predicting OS in melanoma treatment.