Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Emergency Department, Peking University Third Hospital, Peking University School of Medicine, Beijing, 100083, China.
J Transl Med. 2023 Jan 30;21(1):57. doi: 10.1186/s12967-023-03891-4.
Immunotherapy is a vital treatment for patients with cutaneous melanoma (CM), but effective predictors to guide clinical immunotherapy are lacking. Cuproptosis is a newly discovered mode of cell death related to tumorigenesis. Exploring the relationship between the mode of cuproptosis and the effect of immunotherapy on CM could better guide clinical management. We clustered all patients with CM in the Cancer Genome Atlas (TCGA) database based on cuproptosis-related genes (CRGs). Prognosis, immunotherapeutic effect, tumor microenvironment score, expression of CD274, CTLA4, and PDCD1, and abundance of CD8 + T infiltration in group A were higher than in group B. Using a combination of LASSO and COX regression analysis, we identified 10 molecules significant to prognosis from differentially expressed genes between the two groups and constructed a cuproptosis-related scoring system (CRSS). Compared with the American Joint Committee on Cancer (AJCC) staging system, CRSS more accurately stratified CM patient risk and guided immunotherapy. CRSS successfully stratified risk and predicted the effect of immunotherapy in 869 patients with eight CM immunotherapy datasets and multiple other tumor immunotherapy cohorts. The nomogram model, which combined AJCC stage and CRSS, greatly improved the ability and accuracy of prognosis prediction. In general, our cuproptosis-related scoring system and nomogram model accurately stratified risk in CM patients and effectively predicted prognosis and the effect of immunotherapy in CM patients.
免疫疗法是治疗皮肤黑色素瘤 (CM) 患者的重要手段，但缺乏有效的预测指标来指导临床免疫治疗。铜死亡是一种新发现的与肿瘤发生相关的细胞死亡方式。探讨铜死亡方式与 CM 免疫治疗效果之间的关系，可以更好地指导临床管理。我们根据铜死亡相关基因 (CRGs) 将癌症基因组图谱 (TCGA) 数据库中的所有 CM 患者进行聚类。A 组患者的预后、免疫治疗效果、肿瘤微环境评分、CD274、CTLA4 和 PDCD1 的表达以及 CD8+T 浸润的丰度均高于 B 组。通过 LASSO 和 COX 回归分析，我们从两组间差异表达基因中识别出 10 个与预后相关的分子，并构建了铜死亡相关评分系统 (CRSS)。与美国癌症联合委员会 (AJCC) 分期系统相比，CRSS 更准确地对 CM 患者的风险进行分层，并指导免疫治疗。CRSS 成功地对 869 名 CM 免疫治疗患者的 8 个数据集和多个其他肿瘤免疫治疗队列的风险进行了分层，并预测了免疫治疗的效果。联合 AJCC 分期和 CRSS 的列线图模型大大提高了预后预测的能力和准确性。总的来说，我们的铜死亡相关评分系统和列线图模型可以准确地对 CM 患者的风险进行分层，并有效地预测 CM 患者的预后和免疫治疗效果。
