目的:二硫化物凋亡是一种新的与癌症生长相关的代谢相关的调节细胞死亡。本研究旨在探讨皮肤皮肤黑色素瘤(SKCM)中与双硫下垂相关的分子机制,并建立与双硫下垂相关的基因标签,以预测SKCM的预后。
方法:从SKCM的RNA-seq数据中鉴定出二硫化物凋亡相关基因。通过单变量Cox和LASSO分析开发并验证了风险评分签名。此外,研究了与风险评分相关的免疫微环境.最后,建立了一个与二硫键凋亡相关的基因-转录因子-miRNA网络,并在SKCM细胞系中初步验证了5个双硫凋亡相关基因的表达水平。
结果:在SKCM样品中鉴定出107个与二硫键沉积相关的差异表达基因。建立了十个二硫键下垂基因签名,包括BIN2、CCL3L3、CCL8、CD79A、CIITA,CXCR3,DEFB1,GPR171,IL2RB,SOCS1。SKCM样本分为高危组和低危组,其中低危组中的样本显示出更好的生存表现。受试者工作特征曲线分析证实了二硫键下垂相关基因预后模型的良好效能。除DEFB1外,其余9个基因与T细胞CD8+呈正相关,T细胞CD4+记忆激活,T细胞γδ,NK细胞激活,和巨噬细胞M1,它们都与NK细胞静息呈负相关,巨噬细胞M0、巨噬细胞M2和肥大细胞活化。最后,我们在A875和A375中验证了SOCS1和DEFB1的下调水平和CXCR3,BIN2和CCL3L3的上调水平.
结论:我们成功为SKCM患者建立了10个与双硫细胞凋亡相关的基因预测预后特征。
OBJECTIVE: Disulfidptosis is a new metabolic-related regulated cell death associated with cancer growth. This study aimed to investigate the molecular mechanisms associated with disulfidptosis in skin cutaneous melanoma (SKCM) and establish a disulfidptosis-related gene signature for prognostic prediction in SKCM.
METHODS: Disulfidptosis-associated genes were identified from RNA-seq data of SKCM. A risk score signature was developed and validated through univariate Cox and LASSO analyses. Additionally, the immune microenvironment related to the risk score signature was investigated. Finally, a disulfidptosis-related genes-transcription factor -miRNA network was developed, and the expression levels of five disulfidptosis-related genes were initially verified in SKCM cell lines.
RESULTS: A total of 107 disulfidptosis-related differentially expressed genes in SKCM samples were identified. A ten-disulfidptosis-gene signature was established, including BIN2, CCL3L3, CCL8, CD79A, CIITA, CXCR3, DEFB1, GPR171, IL2RB, and SOCS1. The SKCM samples were divided into high- and low-risk groups, of which samples in the low-risk group showed better survival performance. The receiver operating characteristic curve analysis confirmed the good potency of the disulfidptosis-related gene prognostic model. Except for DEFB1, the other nine genes were positively related with T cell CD8+, T cell CD4+ memory activated, T cell gamma delta, NK cell activated, and macrophage M1, and they were all negatively related with NK cell resting, macrophage M0, macrophage M2, and mast cell activated. Finally, we verified downregulated levels of SOCS1 and DEFB1 and upregulated CXCR3, BIN2, and CCL3L3 in A875 and A375.
CONCLUSIONS: We successfully established ten disulfidptosis-related genes\' prediction prognostic signatures for SKCM patients.