Chronic obstructive pulmonary disease (COPD) patients are likely to develop sarcopenia, while the exact mechanism underlying the association between sarcopenia and COPD is still not clear. This cohort study aims to explore the genes, signaling pathways, and transcription factors (TFs) that are related to the molecular pathogenesis of sarcopenia and COPD. According to the strict inclusion criteria, two gene sets (GSE8479 for sarcopenia and GSE76925 for COPD) were obtained from the Gene Expression Omnibus (GEO) platform. Overlapping differentially expressed genes (DEGs) in sarcopenia and COPD were detected, and comprehensive bioinformatics analysis was conducted, including functional annotation, enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), construction of a protein–protein interaction (PPI) network, co-expression analysis, identification and validation of hub genes, and TFs prediction and verification. In total, 118 downregulated and 92 upregulated common DEGs were detected. Functional analysis revealed that potential pathogenesis involves oxidoreductase activity and ferroptosis. Thirty hub genes were detected, and ATP metabolic process and oxidative phosphorylation were identified to be closely related to the hub genes. Validation analysis revealed that SAA1, C3, and ACSS2 were significantly upregulated, whereas ATF4, PPARGC1A, and MCTS1 were markedly downregulated in both sarcopenia and COPD. In addition, six TFs (NFKB1, RELA, IRF7, SP1, MYC, and JUN) were identified to regulate the expression of these genes, and SAA1 was found to be coregulated by NFKB1 and RELA. This study uncovers potential common mechanisms of COPD complicated by sarcopenia. The hub gene SAA1 and the NF-κB signaling pathway could be involved, and oxidative phosphorylation and ferroptosis might be important contributors to this comorbidity.

中文翻译：

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肌肉减少症与慢性阻塞性肺疾病之间病理生理学关联的基因和关键通路的鉴定

慢性阻塞性肺疾病（COPD）患者可能会出现肌肉减少症，而肌肉减少症与慢性阻塞性肺病之间关联的确切机制仍不清楚。本队列研究旨在探讨与肌肉减少症和慢性阻塞性肺病分子发病机制相关的基因、信号通路和转录因子（TF）。根据严格的纳入标准，从基因表达综合（GEO）平台获得了两个基因集（肌少症的GSE8479和COPD的GSE76925）。检测肌肉减少症和慢性阻塞性肺病中重叠的差异表达基因（DEG），并进行全面的生物信息学分析，包括功能注释、基因本体（GO）和京都基因与基因组百科全书（KEGG）的富集分析、蛋白质-蛋白质的构建相互作用（PPI）网络、共表达分析、中心基因的识别和验证以及TF预测和验证。总共检测到 118 个下调和 92 个上调的常见 DEG。功能分析表明潜在的发病机制涉及氧化还原酶活性和铁死亡。检测到30个hub基因，发现ATP代谢过程和氧化磷酸化与hub基因密切相关。验证分析显示，SAA1、C3 和 ACSS2 在肌少症和 COPD 中显着上调，而 ATF4、PPARGC1A 和 MCTS1 显着下调。此外，还确定了 6 个 TF（NFKB1、RELA、IRF7、SP1、MYC 和 JUN）来调节这些基因的表达，并且发现 SAA1 受到 NFKB1 和 RELA 的共同调节。这项研究揭示了慢性阻塞性肺病并发肌肉减少症的潜在共同机制。枢纽基因 SAA1 和 NF-κB 信号通路可能参与其中，氧化磷酸化和铁死亡可能是导致这种合并症的重要因素。