The potential lipid biomarker 5‐HETE for acute exacerbation identified by metabolomics in patients with idiopathic pulmonary fibrosis

特发性肺纤维化 医学 生物标志物 内科学 恶化 脂质代谢 胃肠病学 血脂谱 病理 胆固醇 生物 生物化学
作者
Yichao Zhao,Yanchen Shi,Ji Zhang,Huizhe Zhang,Li Wang,Shufei Wu,Mingrui Zhang,Mengying Liu,Xu Ye,Huimin Gu,Cheng Jiang,Xiaoling Ye,Huihui Zhu,Qi Li,Xinmei Huang,Mengshu Cao
出处
期刊:Respirology [Wiley]
标识
DOI:10.1111/resp.14866
摘要

Abstract Background and Objective Acute exacerbation (AE) is often the fatal complication of idiopathic pulmonary fibrosis (IPF). Emerging evidence indicates that metabolic reprogramming and dysregulation of lipid metabolism are distinctive characteristics of IPF. However, the lipid metabolic mechanisms that underlie the pathophysiology of AE‐IPF remain elusive. Methods Serum samples for pilot study were collected from 34 Controls, 37 stable IPF (S‐IPF) cases and 41 AE‐IPF patients. UHPLC–MS/MS was utilized to investigate metabolic variations and identify lipid biomarkers in serum. ELISA, quantitative PCR and western blot were employed to validate the identified biomarkers. Results There were 32 lipid metabolites and 5 lipid metabolism pathways enriched in all IPF patients compared to Controls. In AE‐IPF versus S‐IPF, 19 lipid metabolites and 12 pathways were identified, with 5‐hydroxyeicosatetraenoic Acid (5‐HETE) significantly elevated in AE‐IPF. Both in internal and external validation cohorts, the serum levels of 5‐HETE were significantly elevated in AE‐IPF patients compared to S‐IPF subjects. Consequently, the indicators related to 5‐HETE in lipid metabolic pathway were significantly changed in AE‐IPF patients compared with S‐IPF cases in the lung tissues. The serum level of 5‐HETE was significantly correlated with the disease severity (CT score and PaO 2 /FiO 2 ratio) and survival time. Importantly, the receiver operating characteristic (ROC) curve, Kaplan–Meier analysis and Multivariate Cox regression analysis demonstrated that 5‐HETE represents a promising lipid biomarker for the diagnosis and prognosis of AE‐IPF. Conclusion Our study highlights lipid reprogramming as a novel therapeutic approach for IPF, and 5‐HETE may be a potential biomarker of AE‐IPF patients.
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