Potential biomarkers of idiopathic pulmonary fibrosis: metabonomics driven lipid profiling.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease. At present, the diagnosis of pulmonary fibrosis relies on high-resolution CT and invasive lung biopsy. In view of the lack of specific serum biomarkers in the diagnosis and monitoring of IPF, it is urgent to adopt an integrated metabolomics analysis strategy to screen and verify specific potential biomarkers, and to establish their translational value in the diagnosis, severity and prognosis of IPF.

Objectives: In this study, an integrated metabolomics analysis strategy was used to screen and validate specific potential biomarkers for the diagnosis and evaluation of IPF severity and prognosis.

Method: In this study, the serum metabolome of the two groups was compared by liquid chromatography-mass spectrometry (LC-MS) to study the characteristics of metabolic changes related to the disease (n = 30) and to screen potential biomarkers. Then multivariate regression analysis and correlation network modeling were used to analyze the correlation between target metabolites and pulmonary function parameters, hematological parameters and coagulation function parameters.

Results: Multiple pathways related to lipid metabolism were enriched in IPF patients compared to controls, including cholesterol metabolism, sphingolipid metabolism, steroid metabolism, and biosynthetic terpenoid metabolism. In addition, 37 compounds related to lipid metabolism were enriched in IPF patients, among which Palmitoyl ethanolamide (PEA) and 2-amino-1,3,4-octadecanetriol were significantly increased. ROC curve analysis, Kaplan-Meier application analysis model and multivariate Cox regression analysis showed that the two potential biomarkers could be used for the diagnosis and prognosis evaluation of IPF.

Conclusion: This study clarified that metabolic reprogramming and lipid metabolism disorder are significant characteristics of IPF. PEA and 2-Amino-1,3,4-octadecanetriol May be potential biomarkers for patients with IPF and have diagnostic and prognostic evaluation value for IPF.

Highlights: Through systematic metabolomics analysis, two novel serum lipid metabolites were identified as potential biomarkers for IPF for the first time. It has been confirmed that IPF patients exhibit significant reprogramming of lipid metabolism. It was the first time that 2-amino-1,3,4-octadecanetriol was reported to have a significant positive correlation with the abnormal coagulation function indicators (APTT, Fib, D-dimer) in patients with IPF. This provides a new metabolic perspective for understanding the pathophysiological mechanism of the increased risk of venous thromboembolism (VTE) in IPF patients. Both of the two potential biomarkers were negatively correlated with hemoglobin. This connects the often overlooked IPF complication of nutritional metabolism imbalance (such as anemia) with the disease-specific metabolic changes, highlighting the importance of paying attention to the nutritional status in the management of IPF.