He Li, Lin Fangmei, Zhou Yawen, Dong Meihua, Deng Mingfang, Li Jing, Jia Nan
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, P.R. China.
Guangzhou National Laboratory, Guangzhou International Bio Island, China.
J Int Med Res. 2025 Apr;53(4):3000605251332204. doi: 10.1177/03000605251332204. Epub 2025 Apr 27.
ObjectiveEmerging evidence has indicated the potential role of DNA damage response in asthma pathogenesis, but the underlying mechanisms remain elusive. Therefore, this study aimed to identify key diagnostic DNA damage response-related genes in asthma and explore their regulatory networks.MethodsDifferentially expressed genes between healthy individuals and patients with asthma were identified using the Gene Expression Omnibus database. Hub DNA damage response-related differentially expressed genes were determined via protein-protein interaction network and verified through gene expression analysis. Receiver operating characteristic curve was employed to identify diagnostic genes. Transcription factor-microRNA-target gene interactions were analyzed to uncover the regulatory networks in asthma pathogenesis. In this observational study, reverse transcription quantitative polymerase chain reaction was used to validate gene expression levels in healthy individuals and patients with asthma.ResultsSix of the nine hub genes (, , , , , and ) were identified as key diagnostic genes. These genes may contribute to asthma progression by regulating inflammatory pathways, such as cyclic GMP-AMP synthase-stimulator of interferon genes, senescence-associated secretory phenotype, autophagy, and apoptosis. Three microRNAs and eleven transcription factors were recognized as potential regulators. Reverse transcription quantitative polymerase chain reaction confirmed the downregulation of DNA damage response genes in asthma and revealed distinct expression patterns across different asthma endotypes.ConclusionSix DNA damage response-related genes may serve as diagnostic biomarkers for asthma, and the transcription factor-microRNA-DNA damage response gene network highlights the role of DNA damage response in asthmatic inflammation.
新出现的证据表明DNA损伤反应在哮喘发病机制中具有潜在作用，但其潜在机制仍不清楚。因此，本研究旨在确定哮喘中关键的诊断性DNA损伤反应相关基因，并探索其调控网络。
利用基因表达综合数据库确定健康个体与哮喘患者之间的差异表达基因。通过蛋白质-蛋白质相互作用网络确定核心DNA损伤反应相关差异表达基因，并通过基因表达分析进行验证。采用受试者工作特征曲线确定诊断基因。分析转录因子-微小RNA-靶基因相互作用，以揭示哮喘发病机制中的调控网络。在这项观察性研究中，采用逆转录定量聚合酶链反应验证健康个体和哮喘患者的基因表达水平。
九个核心基因中的六个（、、、、、和）被确定为关键诊断基因。这些基因可能通过调节炎症途径，如环GMP-AMP合酶-干扰素基因刺激物、衰老相关分泌表型、自噬和凋亡，促进哮喘进展。三个微小RNA和十一个转录因子被认为是潜在的调节因子。逆转录定量聚合酶链反应证实哮喘中DNA损伤反应基因下调，并揭示了不同哮喘亚型之间的不同表达模式。
六个DNA损伤反应相关基因可能作为哮喘的诊断生物标志物，转录因子-微小RNA-DNA损伤反应基因网络突出了DNA损伤反应在哮喘炎症中的作用。
