BackgroundChronic obstructive pulmonary disease (COPD) is a globally prevalent respiratory disease, and programmed cell death plays a pivotal role in the development of COPD. Disulfidptosis is a newly discovered type of cell death that may be associated with the progression of COPD. However, the expression and role of disulfidptosis‐related genes (DRGs) in COPD remain unclear.MethodsThe expression of DRGs was identified by analyzing RNA sequencing (RNA‐seq) data in COPD. Further, COPD patients were classified into two subtypes by unsupervised cluster analysis to reveal their differences in gene expression and immune infiltration. Meanwhile, hub genes associated with disulfidptosis were screened by weighted gene co‐expression network analysis. Subsequently, the hub genes were validated experimentally in cells and animals. In addition, we screened potential therapeutic drugs through the hub genes.ResultsWe identified two distinct molecular clusters and observed significant differences in immune cell populations between them. In addition, we screened nine hub genes, and experimental validation showed that CDC71, DOHH, PDAP1, and SLC25A39 were significantly upregulated in cigarette smoke‐induced COPD mouse lung tissues and bronchial epithelial cells (BEAS‐2B) treated with cigarette smoke extract. Finally, we predicted 10 potential small molecule drugs such as Atovaquone, Taurocholic acid, Latamoxef, and Methotrexate.ConclusionWe highlighted the strong association between COPD and disulfidptosis, with DRGs demonstrating a discriminative capacity for COPD. Additionally, the expression of certain novel genes, including CDC71, DOHH, PDAP1, and SLC25A39, is linked to COPD and may aid in the diagnosis and assessment of this condition.

中文翻译：

---

慢性阻塞性肺疾病二硫键相关基因的网络表达及免疫浸润分析

研究背景慢性阻塞性肺疾病（COPD）是一种全球流行的呼吸系统疾病，程序性细胞死亡在COPD的发生发展中起着关键作用。二硫下垂症是一种新发现的细胞死亡类型，可能与慢性阻塞性肺病的进展有关。然而，二硫下垂相关基因（DRGs）在COPD中的表达和作用仍不清楚。方法通过分析COPD中的RNA测序（RNA-seq）数据来鉴定DRGs的表达。此外，通过无监督聚类分析将COPD患者分为两个亚型，以揭示其基因表达和免疫浸润的差异。同时，通过加权基因共表达网络分析筛选与二硫下垂相关的枢纽基因。随后，中心基因在细胞和动物中进行了实验验证。此外，我们通过枢纽基因筛选了潜在的治疗药物。结果我们鉴定了两个不同的分子簇，并观察到它们之间免疫细胞群的显着差异。此外，我们筛选了 9 个枢纽基因，实验验证表明，在用香烟烟雾提取物处理的香烟烟雾诱导的 COPD 小鼠肺组织和支气管上皮细胞 (BEAS-2B) 中，CDC71、DOHH、PDAP1 和 SLC25A39 显着上调。最后，我们预测了 10 种潜在的小分子药物，如阿托伐醌、牛磺胆酸、拉氧头孢和甲氨蝶呤。结论我们强调了 COPD 和二硫下垂症之间的密切关联，DRG 表现出对 COPD 的区分能力。此外，某些新基因（包括 CDC71、DOHH、PDAP1 和 SLC25A39）的表达与慢性阻塞性肺病有关，可能有助于诊断和评估这种疾病。