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男性慢性阻塞性肺疾病患者肺组织中甘油磷脂和氨基酸代谢紊乱的检测

Detection of the Disorders of Glycerophospholipids and Amino Acids Metabolism in Lung Tissue From Male COPD Patients.

作者信息

Huang Qian, Wu Xiaojie, Gu Yiya, Wang Ting, Zhan Yuan, Chen Jinkun, Zeng Zhilin, Lv Yongman, Zhao Jianping, Xie Jungang

机构信息

Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Respiratory and Critical Care Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China.

出版信息

Front Mol Biosci. 2022 Mar 3;9:839259. doi: 10.3389/fmolb.2022.839259. eCollection 2022.

Abstract

At present, few studies have reported the metabolic profiles of lung tissue in patients with COPD. Our study attempted to analyze the lung metabolome in male COPD patients and to screen the overlapping biomarkers of the lung and plasma metabolomes. We performed untargeted metabolomic analysis of normal lung tissue from two independent sets (the discovery set: 20 male COPD patients and 20 controls and the replication set: 47 male COPD patients and 27 controls) and of plasma samples from 80 male subjects containing 40 COPD patients and 40 controls. We found glycerophospholipids (GPs) and Amino acids were the primary classes of differential metabolites between male COPD patients and controls. The disorders of GPs metabolism and the valine, leucine and isoleucine biosynthesis metabolism pathways were identified in lung discovery set and then also validated in the lung replication set. Combining lung tissue and plasma metabolome, Phytosphingosine and l-tryptophan were two overlapping metabolites biomarkers. Binary logistic regression suggested that phytosphingosine together with l-tryptophan was closely associated with male COPD and showed strong diagnostic power with an AUC of 0.911 (95% CI: 0.8460-0.9765). Our study revealed the metabolic perturbations of lung tissues from male COPD patients. The detected disorders of GPs and amino acids may provide an insight into the pathological mechanism of COPD. Phytosphingosine and l-tryptophan were two novel metabolic biomarkers for differentiating COPD patients and controls.

摘要

目前,鲜有研究报道慢性阻塞性肺疾病(COPD)患者肺组织的代谢谱。我们的研究试图分析男性COPD患者的肺代谢组,并筛选肺和血浆代谢组中的重叠生物标志物。我们对来自两个独立数据集(发现集:20例男性COPD患者和20例对照;复制集:47例男性COPD患者和27例对照)的正常肺组织以及来自80名男性受试者(包括40例COPD患者和40例对照)的血浆样本进行了非靶向代谢组学分析。我们发现甘油磷脂(GPs)和氨基酸是男性COPD患者与对照之间主要的差异代谢物类别。在肺发现集中确定了GPs代谢以及缬氨酸、亮氨酸和异亮氨酸生物合成代谢途径的紊乱,随后在肺复制集中也得到了验证。结合肺组织和血浆代谢组,植物鞘氨醇和L-色氨酸是两种重叠的代谢物生物标志物。二元逻辑回归表明,植物鞘氨醇与L-色氨酸共同与男性COPD密切相关,诊断能力较强,曲线下面积(AUC)为0.911(95%CI:0.8460 - 0.9765)。我们的研究揭示了男性COPD患者肺组织的代谢扰动。检测到的GPs和氨基酸紊乱可能为COPD的病理机制提供见解。植物鞘氨醇和L-色氨酸是区分COPD患者和对照的两种新型代谢生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b45/8927538/8c06bb44704a/fmolb-09-839259-g001.jpg

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