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肺腺癌中铜死亡相关基因在免疫浸润和预后中的综合分析

Comprehensive analysis of cuproptosis-related genes in immune infiltration and prognosis in lung adenocarcinoma.

作者信息

Xiaona Xie, Liu Qianzi, Zhou Xuehua, Liang Rongtao, Yang Shengbo, Xu Min, Zhao Haiyang, Li Chengye, Chen Yanfan, Xueding Cai

机构信息

Department of Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

The Institute of Life Sciences, Wenzhou University, University Town, Wenzhou, Zhejiang, 325035, China.

出版信息

Comput Biol Med. 2023 May;158:106831. doi: 10.1016/j.compbiomed.2023.106831. Epub 2023 Apr 5.

Abstract

Copper-dependent cell death, called cuproptosis, is connected to tumor development, prognosis, and the immune response. Nevertheless, the function of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) remains unknown. This work used R software packages to classify the raw data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases of LUAD patients. Afterward, the connections of the various subgroups, clinical pathological traits, and immune infiltration (IMIF) features with the TME mutation status were explored. Ultimately, a nomogram and calibration curve were developed, aiming at enhancing the clinical application of CRG scores and estimating the survival probability of patients. Moreover, the relationships between cuproptosis and the molecular traits, immune cell infiltration of tumor tissue, prognosis, and clinical treatment of patients were investigated in this work. Subsequently, the CRG score was established to predict overall survival (OS), and its credible predictive ability in LUAD patients was identified. Afterward, a highly credible nomogram was created to contribute to the clinical viability of the CRG score. Furthermore, as demonstrated, gene signatures could be applied in assessing tumor immune cell infiltration, clinical traits, and prognosis. In addition, high tumor mutation burden, immunological activity, and significant survival probability were characterized by low CRG scores, and high CRG scores were related to immunosuppression and stromal pathway activation. The current work also discovered a predictive CRG-related signature for LUAD patients, probably contributing to TME trait clarification and more potent immunotherapy strategy exploration.

摘要

铜依赖性细胞死亡,即铜死亡,与肿瘤发展、预后及免疫反应相关。然而,铜死亡相关基因(CRG)在肺腺癌(LUAD)肿瘤微环境(TME)中的功能仍不清楚。这项研究使用R软件包对来自LUAD患者的癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的原始数据进行分类。随后,探索了不同亚组、临床病理特征及免疫浸润(IMIF)特征与TME突变状态之间的联系。最终,绘制了列线图和校准曲线,旨在加强CRG评分的临床应用并估计患者的生存概率。此外,本研究还调查了铜死亡与患者分子特征、肿瘤组织免疫细胞浸润、预后及临床治疗之间的关系。随后,建立了CRG评分以预测总生存期(OS),并确定了其在LUAD患者中的可靠预测能力。之后,创建了一个高度可靠的列线图,以提高CRG评分的临床可行性。此外,研究表明,基因特征可用于评估肿瘤免疫细胞浸润、临床特征及预后。另外,低CRG评分特征为高肿瘤突变负担、免疫活性及显著的生存概率,而高CRG评分与免疫抑制和基质途径激活相关。目前的研究还发现了一种针对LUAD患者的预测性CRG相关特征,可能有助于阐明TME特征并探索更有效的免疫治疗策略。

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