Table_3_Development of a copper metabolism-related gene signature in lung adenocarcinoma.xlsx

PurposeThe dysregulation of copper metabolism is closely related to the occurrence and progression of cancer. This study aims to investigate the prognostic value of copper metabolism-related genes (CMRGs) in lung adenocarcinoma (LUAD) and its characterization in the tumor microenvironment (TME).MethodsThe differentially expressed CMRGs were identified in The Cancer Genome Atlas (TCGA) of LUAD. The least absolute shrinkage and selection operator regression (LASSO) and multivariate Cox regression analysis were used to establish the copper metabolism-related gene signature (CMRGs), which was also validated in Gene Expression Omnibus (GEO) database (GSE72094). The expression of key genes was verified by quantitative real-time PCR (qRT-PCR). Then, the CMRGS was used to develop a nomogram to predict the 1-year, 3-year, and 5-year overall survival (OS). In addition, differences in tumor mutation burden (TMB), biological characteristics and immune cell infiltration between high-risk and low-risk groups were systematically analyzed. Immunophenoscore (IPS) and an anti-PD-L1 immunotherapy cohort (IMvigor210) were used to verify whether CMRGS can predict the response to immunotherapy in LUAD.Results34 differentially expressed CMRGs were identified in the TCGA dataset, 11 of which were associated with OS. The CMRGS composed of 3 key genes (LOXL2, SLC31A2 and SOD3) had showed good clinical value and stratification ability in the prognostic assessment of LUAD patients. The results of qRT-PCR confirmed the expression of key CMRGs in LUAD and normal tissues. Then, all LUAD patients were divided into low-risk and high-risk groups based on median risk score. Those in the low-risk group had a significantly longer OS than those in the high-risk group (P

本研究旨在探究铜代谢相关基因（CMRGs）在肺腺癌（LUAD）发生发展中的预后价值及其在肿瘤微环境（TME）中的特征。研究方法包括：在LUAD的癌症基因组图谱（TCGA）中识别差异表达的CMRGs，运用最小绝对收缩和选择算子回归（LASSO）和多变量Cox回归分析建立铜代谢相关基因签名（CMRGs），并在基因表达综合数据库（GEO）中的GSE72094数据集中进行验证。通过定量实时PCR（qRT-PCR）验证关键基因的表达。随后，利用CMRGS开发了一套预测1年、3年和5年总生存率（OS）的列线图。此外，系统分析了高风险组和低风险组在肿瘤突变负荷（TMB）、生物学特性和免疫细胞浸润方面的差异。通过免疫表型评分（IPS）和抗PD-L1免疫治疗队列（IMvigor210），验证了CMRGS是否能够预测LUAD对免疫治疗的反应。研究结果显示，在TCGA数据集中鉴定出34个差异表达的CMRGs，其中11个与OS相关。由3个关键基因（LOXL2、SLC31A2和SOD3）组成的CMRGS在LUAD患者的预后评估中表现出良好的临床价值和分层能力。qRT-PCR的结果证实了关键CMRGs在LUAD和正常组织中的表达。然后，根据中位风险评分将所有LUAD患者分为低风险组和高风险组。低风险组的总生存期显著长于高风险组（P