Identification of a cuproptosis-associated gene signature and Peptidylprolyl isomerase C as therapeutic target in cutaneous melanoma

Abstract

Cutaneous melanoma is widely known to be the most lethal of skin tumors. Cuproptosis is a newly discovered cell death form which is related to the process of oxidative phosphorylation. However, the exact involvement of cuproptosis in melanoma is unknown. Our research explored the potential relationship between cuproptosis-related genes with prognosis, immune microenvironments, and treatments of melanoma. The cuproptosis regulators differ substantially in melanoma and normal tissues. Additionally, cuproptosis regulators are associated with melanoma. The newly established cuproptosis-related gene signature (CGS) could effectively predict overall survival (OS) of melanoma, and a novel nomogram combining clinical characteristics with CGS was constructed. Further, CD8 + T cells, Tfh cells, B cells, and myeloid-derived suppressor cells were correlated with the CGS. Among the CGS, Peptidylprolyl isomerase C (PPIC) was most associated with melanoma’s poor prognosis and drug resistance. PPIC can promote melanoma progression by enhancingmelanoma cell invasiveness and decreasing CD8 + T cell activation. The current study revealed the correlation between CGS with melanoma prognosis, immune microenvironment, and drug resistance. Moreover, our study provided new data that supports PPIC as a potential and efficient biomarker for OS prognosis in the treatment of melanoma.