Table2_Identification of cuproptosis-related gene signature to predict prognosis in lung adenocarcinoma.DOCX

Background: Studies have reported that coppers are involved in the tumorigenesis and development of tumor. In herein, we aimed to construct a prognostic classification system for lung adenocarcinoma (LUAD) associated with cuproptosis.Methods: Samples information of LUAD were acquired from The Cancer Genome Atlas (TCGA) and GSE31210 dataset. Cuproptosis-related genes were screened from previous research. ConsensusClusterPlus was applied to determine molecular subtypes, which evaluated by genome analysis, tumor immune microenvironment analysis, immunotherapy, functional enrichment analysis. Furthermore, univariate Cox analysis combined with Lasso analysis were employed to construct a cuproptosis-related risk model for LUAD.Results: 14 genes related to cuproptosis phenotype were identified, and 2 clusters (C1 and C2) were determined. Among which, C1 had better survival outcome, less advanced stages, enhanced immune infiltration and enriched in TCA related pathways. A 7 cuproptosis-associated genes risk model was constructed, and the performance was verified in the GSE31210 dataset. A higher RiskScore was significantly correlated with worse overall survival, advanced stages. Cox survival analysis showed that RiskScore was an independent predictor. High-risk group patients had weakened immune infiltration, less likely to benefit from immunotherapy and was more sensitived to immunotherapy.Conclusion: The cuproptosis-related gene signature could serve as potential prognostic predictors for LUAD patients and may provide clues for the intervention of cuproptosis induced harm and targeted anti-tumor application.

背景：研究指出，铜离子在肿瘤的发生和发展过程中扮演着重要角色。本研究旨在构建一种与铜死亡相关的肺腺癌（LUAD）预后分类系统。方法：收集了来自癌症基因组图谱（TCGA）和GSE31210数据集的肺腺癌样本信息。从先前研究中筛选出与铜死亡相关的基因。采用ConsensusClusterPlus方法确定分子亚型，并通过基因组分析、肿瘤免疫微环境分析、免疫治疗和功能富集分析进行评估。此外，通过单变量Cox分析和Lasso分析构建了与铜死亡相关的风险模型。结果：鉴定出14个与铜死亡表型相关的基因，并确定了2个簇（C1和C2）。其中，C1组具有更好的生存预后、较低的临床分期、增强的免疫浸润和富含TCA相关通路。构建了一个包含7个铜死亡相关基因的风险模型，并在GSE31210数据集中验证了其性能。高风险评分与较差的总生存期和高级别临床分期显著相关。Cox生存分析表明，风险评分是一个独立的预后指标。高风险组患者的免疫浸润减弱，较少从免疫治疗中获益，且对免疫治疗更为敏感。结论：铜死亡相关基因标志物可作为肺腺癌患者的潜在预后预测因子，并可能为铜死亡诱导的损伤干预和靶向抗肿瘤应用提供线索。