Qian Jiahua, Lu Chenghua, Meng Kai, Xu Zhihong, Xue Honghao, Yang Weijie
Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Respiratory Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
PLoS One. 2025 Jan 10;20(1):e0314114. doi: 10.1371/journal.pone.0314114. eCollection 2025.
Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterium that causes severe pulmonary infections. Recent studies indicate that ferroptosis may play a critical role in the pathogenesis of M. abscessus pulmonary disease. We obtained gene expression microarray data from the Gene Expression Omnibus database, focusing on THP-1-derived macrophages infected with M. abscessus and uninfected controls. Differentially expressed genes related to ferroptosis were identified through weighted gene co-expression network analysis and the "limma" package, followed by gene set variation analysis and gene set enrichment analysis for enrichment assessment. To explore regulatory network relationships among hub genes, we constructed RBP-mRNA, ceRNA, and TF-mRNA networks. Additionally, a protein-protein interaction network was built, and functional enrichment analyses were conducted for the hub genes. The diagnostic value of these genes was assessed using receiver operating characteristic curves. Six differentially expressed genes associated with ferroptosis were identified in M. abscessus infection. The receiver operating characteristic curves demonstrated that these genes had excellent predictive value for the infection. Functional enrichment analysis showed that these genes were involved in immune responses, inflammation, cellular metabolism, cell death, and apoptosis. Pathway enrichment analysis revealed significant enrichment in pathways related to apoptosis, inflammation, and hypoxia. The RBP-mRNA network highlighted significant interactions between hub genes and key RNA-binding proteins, while the ceRNA network predicted that miRNAs and lncRNAs regulate ferroptosis-related genes NACC2 and ITPKB. Furthermore, interactions between the hub gene HSD3B7 and transcription factors LMNB1 and ASCL1 may promote ferroptosis in macrophages by influencing iron metabolism and reactive oxygen species production, contributing to the M. abscessus infection process. Our findings identified biomarkers linked to ferroptosis in M. abscessus infection, providing new insights into its pathogenic mechanisms and potential therapeutic strategies.
脓肿分枝杆菌是一种快速生长的非结核分枝杆菌，可引起严重的肺部感染。最近的研究表明，铁死亡可能在脓肿分枝杆菌肺病的发病机制中起关键作用。我们从基因表达综合数据库中获取了基因表达微阵列数据，重点关注感染脓肿分枝杆菌的THP-1衍生巨噬细胞和未感染的对照。通过加权基因共表达网络分析和“limma”软件包鉴定与铁死亡相关的差异表达基因，随后进行基因集变异分析和基因集富集分析以进行富集评估。为了探索枢纽基因之间的调控网络关系，我们构建了RBP-mRNA、ceRNA和TF-mRNA网络。此外，构建了蛋白质-蛋白质相互作用网络，并对枢纽基因进行了功能富集分析。使用受试者工作特征曲线评估这些基因的诊断价值。在脓肿分枝杆菌感染中鉴定出6个与铁死亡相关的差异表达基因。受试者工作特征曲线表明，这些基因对感染具有出色的预测价值。功能富集分析表明，这些基因参与免疫反应、炎症、细胞代谢、细胞死亡和凋亡。通路富集分析显示在与凋亡、炎症和缺氧相关的通路中存在显著富集。RBP-mRNA网络突出了枢纽基因与关键RNA结合蛋白之间的显著相互作用，而ceRNA网络预测miRNA和lncRNA调节铁死亡相关基因NACC2和ITPKB。此外，枢纽基因HSD3B7与转录因子LMNB1和ASCL1之间的相互作用可能通过影响铁代谢和活性氧的产生来促进巨噬细胞中的铁死亡，从而促进脓肿分枝杆菌的感染过程。我们的研究结果确定了与脓肿分枝杆菌感染中铁死亡相关的生物标志物，为其致病机制和潜在治疗策略提供了新的见解。
