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高覆盖脂质组学分析揭示了用于诊断慢性阻塞性肺疾病急性加重的生物标志物。

High-coverage lipidomics analysis reveals biomarkers for diagnosis of acute exacerbation of chronic obstructive pulmonary disease.

机构信息

Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases co-constructed by Henan Province & Education Ministry of P.R. China, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, PR China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, PR China.

Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases co-constructed by Henan Province & Education Ministry of P.R. China, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, PR China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, PR China; The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, PR China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Jun 30;1201-1202:123278. doi: 10.1016/j.jchromb.2022.123278. Epub 2022 May 5.

DOI:10.1016/j.jchromb.2022.123278
PMID:35561641
Abstract

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading cause of morbidity and mortality in COPD management. However, detecting the progression from the stable stage to acute exacerbation mainly depends on doctors' judgment of clinical symptoms, and there is no biomarker that can be used for auxiliary clinical diagnosis. In this work, serum samples from COPD patients (n = 82) and healthy subjects (n = 29) were collected and analyzed. Patients with COPD were divided into stable COPD (SCOPD) and AECOPD groups, with the latter comprising subtypes 1 and 2. High-coverage lipidomics profiling of 913 lipids belonging to 19 subclasses was carried out by liquid chromatography-Q-Exactive orbitrap mass spectrometry. We performed 4 cross-comparisons to characterize metabolic disturbances associated with the progression of stable COPD to AECOPD-ie, SCOPD vs healthy subjects, AECOPD vs SCOPD, AECOPD subtype 1 vs SCOPD, and AECOPD subtype 2 vs SCOPD. We tentatively identified 86 lipids with differential abundance among groups, lipids that were altered from the stable stage of disease to AECOPD included sphingolipids, ether-containing glycerophospholipids, phosphatidylglycerols, and glycerol lipids. Three panels of lipid biomarkers specific to AECOPD, AECOPD subtypes 1 and 2 vs SCOPD yielded areas under the receiver operating characteristic curve of 0.788, 0.921 and 0.920, respectively, with sensitivity of 77.5%, 80.7% and 91.3%, respectively, and specificity of 75.8%, 97.0% and 87.9%, respectively. The result indicated differences in lipid metabolism may underlie AECOPD and its 2 subtypes and can serve as biomarkers for early diagnosis, and high-coverage lipidomics proved to be an accurate approach to profile the lipid metabolism in biological samples.

摘要

慢性阻塞性肺疾病(COPD)的急性加重(AECOPD)是 COPD 管理中发病率和死亡率的主要原因。然而,从稳定期到急性加重的进展主要依赖于医生对临床症状的判断,目前还没有可用于辅助临床诊断的生物标志物。在这项工作中,收集了 COPD 患者(n=82)和健康受试者(n=29)的血清样本并进行了分析。将 COPD 患者分为稳定型 COPD(SCOPD)和 AECOPD 组,后者包括亚型 1 和 2。通过液相色谱-Q-Exactive 轨道阱质谱法对属于 19 个亚类的 913 种脂质进行了高覆盖率脂质组学分析。我们进行了 4 次交叉比较,以表征与稳定期 COPD 向 AECOPD 进展相关的代谢紊乱,即 SCOPD 与健康受试者、AECOPD 与 SCOPD、AECOPD 亚型 1 与 SCOPD、AECOPD 亚型 2 与 SCOPD。我们初步确定了 86 种组间差异丰度的脂质,从疾病的稳定期到 AECOPD 发生变化的脂质包括鞘脂、醚型甘油磷脂、磷脂酰甘油和甘油脂质。AECOPD、AECOPD 亚型 1 和 2 与 SCOPD 特异性的三组脂质生物标志物的曲线下面积分别为 0.788、0.921 和 0.920,敏感性分别为 77.5%、80.7%和 91.3%,特异性分别为 75.8%、97.0%和 87.9%。结果表明,脂质代谢的差异可能是 AECOPD 及其 2 个亚型的基础,可以作为早期诊断的生物标志物,高覆盖率脂质组学被证明是一种准确的方法,可以对生物样本中的脂质代谢进行分析。

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