Identification of the lipid biomarkers from plasma in idiopathic pulmonary fibrosis by Lipidomics

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible interstitial pulmonary disease featured by high mortality, chronic and progressive course, and poor prognosis with unclear etiology. Currently, more studies have been focusing on identifying biomarkers to predict the progression of IPF, such as genes, proteins, and lipids. Lipids comprise diverse classes of molecules and play a critical role in cellular energy storage, structure, and signaling. The role of lipids in respiratory diseases, including cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD) has been investigated intensely in the recent years. The human serum lipid profiles in IPF patients however, have not been thoroughly understood and it will be very helpful if there are available molecular biomarkers, which can be used to monitor the disease progression or provide prognostic information for IPF disease.

Methods: In this study, we performed the ultraperformance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) to detect the lipid variation and identify biomarker in plasma of IPF patients. The plasma were from 22 IPF patients before received treatment and 18 controls.

Results: A total of 507 individual blood lipid species were determined with lipidomics from the 40 plasma samples including 20 types of fatty acid, 159 types of glycerolipids, 221 types of glycerophospholipids, 47 types of sphingolipids, 46 types of sterol lipids, 7 types of prenol lipids, 3 types of saccharolipids, and 4 types of polyketides. By comparing the variations in the lipid metabolite levels in IPF patients, a total of 62 unique lipids were identified by statistical analysis including 24 kinds of glycerophoslipids, 30 kinds of glycerolipids, 3 kinds of sterol lipids, 4 kinds of sphingolipids and 1 kind of fatty acids. Finally, 6 out of 62 discriminating lipids were selected as the potential biomarkers, which are able to differentiate between IPF disease and controls with ROC analysis.

Conclusions: Our results provided vital information regarding lipid metabolism in IPF patients and more importantly, a few potentially promising biomarkers were firstly identified which may have a predictive role in monitoring and diagnosing IPF disease.

Keywords: Biomarkers; Idiopathic pulmonary fibrosis; Lipid; Lipidomics; Plasma.

Fig. 1

a. OPLS-DA scores plot based on the plasma lipid profiling of IPF patients (●D) and controls (●NC). b. S-plot used in the lipid biomarkers selection. The lipids marked (□) are the lipids selected as potential biomarkers

Fig. 2

Correlation analysis of the 35 pre-selected discriminating lipids in IPF patients and controls. R1 to R35 represents the corresponding pre-selected discriminating lipids as shown in Table 2. Red and blue represent a negative and positive correlation, respectively. The color depth represents the degree of correlation: the deeper color indicates higher correlation

Fig. 3

ROC curves analysis of 12 lipid metabolite for discriminating IPF objects from controls