CDKN2A, a key gene in copper-induced cell death model, influencing melanoma invasion and apoptosis.

Abstract

Skin cutaneous melanoma (SKCM) is one of the most lethal cancers translating into 75% of skin cancer-related deaths. Despite the advances in SKCM management and treatment strategies, the overall survival of patients remains unsatisfactory due to the metastatic properties of SKCM as well as the absence of effective prognostic biomarkers. Recent studies have shown that overload copper renders accumulation of mitochondrial proteins and fuels a form of cell death at odds with known death mechanisms and is hinged on mitochondrial respiration, the so-called cuproptosis. However, the exact role of cuproptosis in SKCM development and progression is unknown, and painting a clear picture of its functions in SKCM is fraught with challenges. A more systematic investigation is justified. In this study, we were posed to dissect the clout and latent regulatory mechanisms of cuproptosis-related genes (CRGs) in reining in SKCM progression. Also, we identified three CRGs that stood out were used to construct a prognostic model, which could be employed to predict the prognosis of patients with SKCM. Finally, through pan-cancer analysis, we found that the four cuproptosis key genes play a role in multiple tumors, suggesting that cuproptosis may impact tumor progression at the pan-cancer level. Taken together, these findings may not only contribute to the development of treatment strategies but also provide clues for treatment decision-making.