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通过机器学习算法鉴定慢性阻塞性肺疾病中与端粒维持相关的生物标志物和调控机制。

Identification of telomere maintenance related biomarkers and regulatory mechanisms in chronic obstructive pulmonary disease by machine learning algorithm.

作者信息

Cao Haiyan, Chu Xiangjian

机构信息

Department of Respiratory and Critical Care, Rugao People's Hospital, Nantong, 226500, Jiangsu, China.

出版信息

Sci Rep. 2025 Jul 22;15(1):26614. doi: 10.1038/s41598-025-11347-6.

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease that accelerates the aging process of the lung. Despite advancements in managing symptoms and preventing acute exacerbations, significant gaps remain in our understanding of the complex mechanisms that drive disease progression and contribute to mortality in COPD. In our work, we have successfully identified a set of five robust biomarkers (including RMI1, RAD51, RAD52, SNRNP70 and CHEK1). These biomarkers effectively distinguish COPD samples from normal samples, with area under the curve (AUC) value greater than 0.65 in the training set and greater than 0.80 in the validation set. Gene set enrichment analysis (GSEA) analysis showed that the main enrichment pathways were Non-alcoholic fatty liver disease, Spliceosome, Oxidative phosphorylation, etc. We also found these five genes had high accuracy in the diagnosis of COPD in both the training and verification sets. Molecular docking showed that the TOP5 small drug molecules acting with CHEK1 were U-0126, KN-62, BX-912, LY-294,002 and AZD-7762. The results of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) showed that there were significant differences in the expression of SNRNP70 and RAD52 between COPD and control samples (p < 0.05).

摘要

慢性阻塞性肺疾病(COPD)是一种进行性呼吸系统疾病,会加速肺部的老化过程。尽管在症状管理和预防急性加重方面取得了进展,但我们对驱动COPD疾病进展并导致其死亡的复杂机制的理解仍存在重大差距。在我们的研究中,我们成功鉴定出一组五个强大的生物标志物(包括RMI1、RAD51、RAD52、SNRNP70和CHEK1)。这些生物标志物能有效区分COPD样本和正常样本,在训练集中曲线下面积(AUC)值大于0.65,在验证集中大于0.80。基因集富集分析(GSEA)表明主要富集途径为非酒精性脂肪性肝病、剪接体、氧化磷酸化等。我们还发现这五个基因在训练集和验证集中对COPD的诊断具有较高的准确性。分子对接显示与CHEK1相互作用的TOP5小药物分子为U-0126、KN-62、BX-912、LY-294,002和AZD-7762。实时逆转录聚合酶链反应(RT-qPCR)结果显示,COPD样本和对照样本中SNRNP70和RAD52的表达存在显著差异(p < 0.05)。

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