Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China.
Hubei Engineering Research Center of Skin Disease Theranostics and Health, Wuhan, China.
Pigment Cell Melanoma Res. 2024 Nov;37(6):864-880. doi: 10.1111/pcmr.13185. Epub 2024 Aug 8.
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 CD8T 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 CD8T 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.
皮肤黑色素瘤是所有皮肤肿瘤中最致命的一种。最近，铜死亡，一种与氧化磷酸化有关的新型细胞死亡形式，已成为一个重要因素。然而，铜死亡在黑色素瘤中的确切作用尚不清楚。我们的研究探讨了铜死亡相关基因、预后、免疫微环境与黑色素瘤治疗之间的潜在联系。值得注意的是，铜死亡调节剂在黑色素瘤和正常组织之间表现出显著差异，这表明它们与黑色素瘤有关。新开发的铜死亡相关基因特征（CGS）在黑色素瘤中表现出强大的总体生存（OS）预测能力。我们构建了一个新的列线图，将临床特征与 CGS 相结合，以提高预测准确性。此外，该研究还揭示了 CGS 与免疫细胞群之间的相关性，包括 CD8T 细胞、滤泡辅助 T 细胞（Tfh 细胞）、B 细胞和髓系来源的抑制细胞。在 CGS 中，肽基脯氨酰顺反异构酶 C（PPIC）被确定为与黑色素瘤预后不良和耐药性最相关的基因。PPIC 被确定为黑色素瘤进展的促进因子，增强细胞侵袭性，同时抑制 CD8T 细胞激活。这项综合性研究不仅阐明了 CGS、黑色素瘤预后、免疫微环境和耐药性之间的复杂联系，还提供了有力的证据支持 PPIC 作为预测黑色素瘤治疗中 OS 的有前途的生物标志物。
