BackgroundsLung adenocarcinoma (LUAD) is the most common subtype of lung cancer, which is the leading cause of cancer death. Dysregulation of cell proliferation and death plays a crucial role in the development of LUAD. As of recently, the role of a new form of cell death, cuproptosis, and it has attracted more and more attention. As of yet, it is not clear whether cuproptosis is involved in the progression of LUAD.MethodsAn integrated set of bioinformatics tools was utilized to analyze the expression and prognostic significance of cuproptosis-related genes. Meanwhile, a robust risk signature was developed using machine learning based on prognostic cuproptosis-related genes and explored the value of prognostic cuproptosis-related signature for clinical applications, functional enrichment and immune landscape. Lastly, the dysregulation of the cuproptosis-related genes in LUAD was validated by in vitro experiment.ResultsIn this study, first, cuproptosis-related genes were found to be differentially expressed in LUAD patients of public databases, and nine of them had prognostic value. Next, a cuproptosis-related model with five features (DLTA, MTF1, GLS, PDHB and PDHA1) was constructed to separate the patients into high- and low-risk groups based on median risk score. Internal validation set and external validation set were used for model validation and evaluation. What’s more, Enrichment analysis of differential genes and the WGCNA identified that cuproptosis-related signatures affected tumor prognosis by influencing tumor immunity. Small molecule compounds were predicted based on differential expressed genes to improve poor prognosis in the high-risk group and a nomogram was constructed to further advance clinical applications. In closing, our data showed that FDX1 affected the prognosis of lung cancer by altering the expression of cuproptosis-related signature.ConclusionA new cuproptosis-related signature for survival prediction was constructed and validated by machine learning algorithm and in vitro experiments to reflect tumor immune infiltration in LUAD patients. The purpose of this article was to provide a potential diagnostic and therapeutic strategy for LUAD.

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铜凋亡相关基因在肺腺癌中的作用

背景肺腺癌 (LUAD) 是最常见的肺癌亚型，是癌症死亡的主要原因。细胞增殖和死亡的失调在 LUAD 的发展中起着至关重要的作用。截至最近，一种新的细胞死亡形式——铜凋亡，其作用越来越受到人们的关注。到目前为止，尚不清楚铜下垂是否参与了 ​​LUAD 的进展。方法利用一套完整的生物信息学工具来分析铜下垂相关基因的表达和预后意义。同时，使用基于预后铜凋亡相关基因的机器学习开发了一个稳健的风险特征，并探索了预后相关特征在临床应用、功能富集和免疫景观方面的价值。最后，体外实验结果本研究首先在公共数据库的LUAD患者中发现了铜细胞凋亡相关基因的差异表达，其中9个基因具有预后价值。接下来，构建了具有五个特征（DLTA、MTF1、GLS、PDHB 和 PDHA1）的铜细胞凋亡相关模型，根据中位风险评分将患者分为高风险组和低风险组。内部验证集和外部验证集用于模型验证和评估。更重要的是，差异基因的富集分析和 WGCNA 发现与铜细胞凋亡相关的特征通过影响肿瘤免疫来影响肿瘤预后。基于差异表达基因预测小分子化合物以改善高危人群的不良预后，并构建诺模图以进一步推进临床应用。最后，体外反映 LUAD 患者肿瘤免疫浸润的实验。本文的目的是为 LUAD 提供潜在的诊断和治疗策略。