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用于慢性阻塞性肺疾病诊断的唾液代谢物谱分析:一项探索性研究。

Salivary metabolites profiling for diagnosis of COPD: an exploratory study.

作者信息

Zherong Zhang, Yan Lv, Meng Gong, Juan Li, Yayun Zhang, Songze Wu, Yu Zhang, Deyun Cheng, Tao Fan

机构信息

Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Division of Internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China hospital, Sichuan university, Chengdu, People's Republic of China.

出版信息

J Breath Res. 2025 Mar 13;19(2). doi: 10.1088/1752-7163/adba07.

Abstract

Pulmonary function tests (PFTs) are the gold standard for diagnosing of Chronic obstructive pulmonary disease (COPD). Given its limitation in some scenarios, it is imperative to develop new high-throughput screening methods for biomarkers in diagnosing COPD. This study aims to explore the feasibility of screening novel diagnostic biomarkers based on salivary metabolomics for the limited availability of PFTs and difficulties in implementation at primary care facilities. Participants were recruited from the outpatient department of West China Hospital. Saliva samples were collected to analyze the metabolites through the UPLC-Q-Exactive Orbitrap-MS platform. The raw data from the mass spectrometer was preprocessed with R software after peak extraction. The Wilcoxon rank sum test, Fold change analysis, PCA and orthogonal partial least squares - discriminant analysis were used to identify potential biomarkers. The receiver operating characteristic curve was used to assess the diagnostic efficacy of the predictive model generated by potential biomarkers. Saliva samples were collected from 66 patients with COPD and 55 healthy volunteers. Significant differences in the salivary metabolome between COPD patients and healthy controls were identified, with 261 differential metabolites recognized, 16 of which were considered as potential biomarker. The diagnostic model generated by these 16 biomarkers can successfully distinguish COPD patients from healthy people. Salivary metabolomic profiling is likely to emerge as a promising method for screening potential diagnostic biomarkers of COPD. Further prospective studies with large sample size are needed to verify the predictive value of these biomarkers in COPD diagnosis.The study is registered with the China Clinical Trial Registry (www.chictr.org.cn/searchprojEN.html) on 26 September 2022, registration number: ChiCTR2200064091.

摘要

肺功能测试(PFTs)是诊断慢性阻塞性肺疾病(COPD)的金标准。鉴于其在某些情况下的局限性,开发用于COPD诊断生物标志物的新型高通量筛选方法势在必行。本研究旨在探讨基于唾液代谢组学筛选新型诊断生物标志物的可行性,因为PFTs可用性有限且在基层医疗机构实施存在困难。研究对象从华西医院门诊部招募。收集唾液样本,通过超高效液相色谱-四极杆-静电场轨道阱质谱平台分析代谢物。质谱仪的原始数据在峰提取后用R软件进行预处理。采用Wilcoxon秩和检验、倍数变化分析、主成分分析和正交偏最小二乘判别分析来识别潜在生物标志物。采用受试者工作特征曲线评估潜在生物标志物生成的预测模型的诊断效能。收集了66例COPD患者和55名健康志愿者的唾液样本。确定了COPD患者与健康对照者唾液代谢组存在显著差异,识别出261种差异代谢物,其中16种被视为潜在生物标志物。由这16种生物标志物生成的诊断模型能够成功区分COPD患者和健康人。唾液代谢组学分析可能成为筛选COPD潜在诊断生物标志物的一种有前景的方法。需要进一步进行大样本量的前瞻性研究来验证这些生物标志物在COPD诊断中的预测价值。该研究于2022年9月26日在中国临床试验注册中心(www.chictr.org.cn/searchprojEN.html)注册,注册号:ChiCTR2200064091。

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