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Development of a copper metabolism-related gene signature in lung adenocarcinoma

作者:Wuguang Chang, Hongmu Li, Leqi Zhong, Tengfei Zhu, Zeng-Hao Chang, Wei Ou, Siyu Wang · 发表于:Frontiers in Immunology · 年份:2022 · DOI:10.3389/fimmu.2022.1040668 · 被引用次数:47 · 研究领域:Ferroptosis and cancer prognosis、Trace Elements in Health、Cancer Immunotherapy and Biomarkers

Purpose: The 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). Methods: The 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. Results: 34 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 o...