Sun Yuming, Lei Shaorong, Luo Xiangyue, Jiang Chufeng, Li Zhexuan
Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Front Pharmacol. 2023 Apr 17;14:1129544. doi: 10.3389/fphar.2023.1129544. eCollection 2023.
Skin cutaneous melanoma (SKCM) is one of the most common cutaneous malignancies, which incidence is increasing. Cuproptosis is a new type of programming cell death recently reported, which may affect the progression of SKCM. The mRNA expression data of melanoma were obtained from the Gene Expression Omnibus and the Cancer Genome Atlas databases. We constructed a prognostic model according to the cuproptosis-related differential genes in SKCM. Finally, real-time quantitative PCR was performed to verify the expression of cuproptosis-related differential genes in patients with different stages of cutaneous melanoma. We detected 767 cuproptosis-related differential genes based on 19 cuproptosis-related genes, and screened out 7 differential genes to construct a prognostic model, which including three high-risk differential genes (SNAI2, RAP1GAP, BCHE), and four low-risk differential genes (JSRP1, HAPLN3, HHEX, ERAP2). Kaplan-Meier analysis indicated that SKCM patients with low-risk differential genes signals had better prognosis. The Encyclopedia of Genomes results manifested that cuproptosis-related differential genes are not only involved in T cell receptor signaling channel, natural killer cell mediated cytotoxicity, but also chemokine signaling pathway and B cell receptor signaling pathway. In our risk scoring model, the receiver operating characteristic (ROC) values of the three-time nodes are 0.669 (1-year), 0.669 (3-year) and 0.685 (5-year), respectively. Moreover, the tumor burden mutational and immunology function, cell stemness characteristics and drug sensitivity have significant differences between low-risk group and high-risk group. The mRNA level of SNAI2, RAP1GAP and BCHE in stage Ⅲ+Ⅳ SKCM patients was significantly higher than that in stage Ⅰ+Ⅱ patients, while the level of JSRP1, HAPLN3, HHEX and ERAP2 in stage Ⅰ+Ⅱ SKCM patients was more remarkable higher than that in stage Ⅲ+Ⅳ SKCM patients. In summary, we suggest that cuproptosis can not only regulate the tumor immune microenvironment but also affect the prognosis of SKCM patients, and may offer a basic theory for SKCM patients survival studies and clinical decision-making with potentially therapeutic drugs.
皮肤黑色素瘤（SKCM）是最常见的皮肤恶性肿瘤之一，其发病率正在上升。铜死亡是最近报道的一种新型程序性细胞死亡，可能影响SKCM的进展。黑色素瘤的mRNA表达数据来自基因表达综合数据库和癌症基因组图谱数据库。我们根据SKCM中与铜死亡相关的差异基因构建了一个预后模型。最后，进行实时定量PCR以验证不同阶段皮肤黑色素瘤患者中与铜死亡相关的差异基因的表达。我们基于19个与铜死亡相关的基因检测到767个与铜死亡相关的差异基因，并筛选出7个差异基因构建预后模型，其中包括3个高风险差异基因（SNAI2、RAP1GAP、BCHE）和4个低风险差异基因（JSRP1、HAPLN3、HHEX、ERAP2）。Kaplan-Meier分析表明，具有低风险差异基因信号的SKCM患者预后较好。基因组百科全书结果表明，与铜死亡相关的差异基因不仅参与T细胞受体信号通路、自然杀伤细胞介导的细胞毒性，还参与趋化因子信号通路和B细胞受体信号通路。在我们的风险评分模型中，三个时间节点的受试者工作特征（ROC）值分别为0.669（1年）、0.669（3年）和0.685（5年）。此外，低风险组和高风险组在肿瘤负荷突变和免疫功能、细胞干性特征以及药物敏感性方面存在显著差异。Ⅲ+Ⅳ期SKCM患者中SNAI2、RAP1GAP和BCHE的mRNA水平显著高于Ⅰ+Ⅱ期患者，而Ⅰ+Ⅱ期SKCM患者中JSRP1、HAPLN3、HHEX和ERAP2的水平显著高于Ⅲ+Ⅳ期SKCM患者。总之，我们认为铜死亡不仅可以调节肿瘤免疫微环境，还可以影响SKCM患者的预后，并可能为SKCM患者的生存研究和使用潜在治疗药物的临床决策提供基础理论。
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