ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1570992
This article is part of the Research TopicCommunity Series in Research Advances of Tuberculosis Vaccine and its Implication on COVID-19: Volume IIIView all 5 articles
Experimental Validation of Cuproptosis-Associated Molecular Signatures and Their Immunological Implications in Pulmonary Tuberculosis
Provisionally accepted
Xiaofang Liu
Qianqian MaZhiming Li
Yong Xue
Jie MiYuxi LiChunfeng BaiDonglin GuoYinping Liu
Yan Liang*
Jianqin Liang*
Xueqiong Wu*- The Eighth Medical Center of PLA General Hospital, Beijing, China
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Background: The pathogenic mechanism underlying Mycobacterium tuberculosis (MTB) remains elusive, posing challenges to its diagnosis and treatment. Cuproptosis is a newly identified mechanism of cell death. This study explores the role of cuproptosis-related genes (CRGs) in pulmonary tuberculosis (PTB) to uncover potential diagnostic biomarkers and therapeutic targets.Methods: Differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were carried out using the GSE83456 dataset. PTB-associated DEGs were intersected with CRGs to identify PTB-related CRGs. Subsequent analyses included functional enrichment, gene interaction, and protein-protein interaction (PPI) network construction. Hub CRGs were screened out via least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms. Diagnostic models were subsequently constructed and validated. The associations of immune cell infiltration and pathway with the identified hub genes were evaluated through single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Hub gene expressions were validated in the GSE42834 and GSE89403 datasets, as well as by RT-qPCR and Western blot (WB) in PTB and extrapulmonary tuberculosis (EPTB) patients. The GSE89403 dataset and gene expression profiling were leveraged to analyze the differential expression of hub genes and their dynamic changes during treatment.Results: Seven PTB-related CRGs were significantly upregulated, were significantly upregulated, among which ASPHD2, GK, and GCH1 were identified as hub genes. These genes exhibited high expression levels in patients with PTB and EPTB, with marked reductions observed following treatment. Notable alterations in immune cell infiltration and immune function in PTB patients were closely related to these hub genes, suggesting activation of innate immune responses and suppression of adaptive immune function. Conclusion: The cuproptosis hub genes ASPHD2, GK, and GCH1 influence the pathogenesis of PTB, and possibly serve as novel diagnostic biomarkers and therapeutic targets.
Keywords: pulmonary tuberculosis, cuproptosis, gene expression analysis, Immune dysregulation, experimental validation
Received: 06 Feb 2025; Accepted: 27 Jun 2025.
Copyright: © 2025 Liu, Ma, Li, Xue, Mi, Li, Bai, Guo, Liu, Liang, Liang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yan Liang, The Eighth Medical Center of PLA General Hospital, Beijing, China
Jianqin Liang, The Eighth Medical Center of PLA General Hospital, Beijing, China
Xueqiong Wu, The Eighth Medical Center of PLA General Hospital, Beijing, China
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