Kuang Junjie, Zheng Zemao, Ma Wen, Zeng Shaohui, Wu Dehua, Weng Xie, Chen Yuming
Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, China.
Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Front Pharmacol. 2023 Sep 15;14:1240736. doi: 10.3389/fphar.2023.1240736. eCollection 2023.
Trace elements such as copper are essential for human health. Recently the journal Nat Rev Cancer has put forward the concept of Cuproplasia, a way of promoting tumor growth through reliance on copper. We attempted to conduct a comprehensive analysis of Cuproplasia-related genes in lung adenocarcinoma (LUAD) to explore the mechanism of action of Cuproplasia-related genes in LUAD. Transcriptome data and clinical information of LUAD were obtained from TCGA-LUAD and GSE31210, and prognostic models of Cuproplasia-related genes were constructed and verified by regression analysis of GSVA, WGCNA, univariate COX and lasso. The signal pathways affected by Cuproplasia-related genes were analyzed by GO, KEGG and hallmarK pathway enrichment methods. Five immunocell infiltration algorithms and IMVIGOR210 data were used to analyze immune cell content and immunotherapy outcomes in the high-low risk group. In the results of WGCNA, BROWN and TURQUOISE were identified as modules closely related to Cuproplasia score. In the end, lasso regression analysis established a Cuproplasia-related signature (CRS) based on 24 genes, and the prognosis of high-risk populations was worse in TCGA-LUAD and GSE31210 datasets. The enrichment analysis showed that copper proliferation was mainly through chromosome, cell cycle, dna replication, g2m checkpoint and other pathways. Immunoinfiltration analysis showed that there were differences in the content of macrophages among the four algorithms. And IMVIGOR210 found that the lower the score, the more effective the immunotherapy was. The Cuproplasia related gene can be used to predict the prognosis and immunotherapy outcome of LUAD patients, and may exert its effect by affecting chromosome-related pathways and macrophages.
铜等微量元素对人体健康至关重要。最近,《自然综述:癌症》杂志提出了铜质增生的概念,即一种通过依赖铜来促进肿瘤生长的方式。我们试图对肺腺癌(LUAD)中与铜质增生相关的基因进行全面分析,以探究与铜质增生相关的基因在LUAD中的作用机制。从TCGA-LUAD和GSE31210获取LUAD的转录组数据和临床信息,并通过GSVA、WGCNA、单变量COX和套索回归分析构建并验证与铜质增生相关基因的预后模型。通过GO、KEGG和hallmarK通路富集方法分析受与铜质增生相关基因影响的信号通路。使用五种免疫细胞浸润算法和IMVIGOR210数据来分析高低风险组中的免疫细胞含量和免疫治疗结果。在WGCNA的结果中,BROWN和TURQUOISE被确定为与铜质增生评分密切相关的模块。最后,套索回归分析基于24个基因建立了与铜质增生相关的特征(CRS),在TCGA-LUAD和GSE31210数据集中,高风险人群的预后较差。富集分析表明,铜增殖主要通过染色体、细胞周期、DNA复制、G2M检查点等途径。免疫浸润分析表明,四种算法中巨噬细胞的含量存在差异。并且IMVIGOR210发现,评分越低,免疫治疗效果越好。与铜质增生相关的基因可用于预测LUAD患者的预后和免疫治疗结果,并可能通过影响与染色体相关的途径和巨噬细胞发挥作用。