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

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

doi:10.3389/fmolb.2022.839259

Abstract

Background: 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. Methods: 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. Results: 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). Conclusion: 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.

Highlights

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airway
No matter in which set, there were no significant differences in sex, age, BMI or smoking status between COPD patients and controls, while there were significant differences in FEV1% predicted and FEV1/FVC% except for a little difference of age in discovery set
Glycerophospholipid metabolism and the valine, leucine and isoleucine biosynthesis pathways were significantly disrupted in COPD patients

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airway. COPD is a heterogeneous disease with complicated pathogenic mechanism which has not been fully elucidated. A large number of genes and protein molecules have been determined to be associated with COPD (Stockley et al, 2019). Metabolites associated with diseases work as the promising biomarker for disease screening, and provide an insight into the pathogenesis of disease (Arakaki et al, 2008). Researches identifying promising metabolite biomarkers to screen patients with COPD and to elucidate the pathogenic mechanisms associated with metabolites are warranted. 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

Methods

Results

Discussion

Conclusion