Serum metabolic profiling identified a distinct metabolic signature in patients with idiopathic pulmonary fibrosis - a potential biomarker role for LysoPC.
- Rindlisbacher B University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, CH-3010, Bern, Switzerland.
- Schmid C Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
- Geiser T Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
- Bovet C University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, CH-3010, Bern, Switzerland. cedric.bovet@insel.ch.
- Funke-Chambour M Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
- 2018-01-12
Published in:
- Respiratory research. - 2018
High-resolution mass spectrometry
Idiopathic pulmonary fibrosis
Lysophosphatidylcholine
Metabolomics
Serum
Ultra high-performance liquid chromatography
Adult
Aged
Biomarkers
Cohort Studies
Female
Humans
Idiopathic Pulmonary Fibrosis
Lysophosphatidylcholines
Male
Metabolomics
Middle Aged
Pilot Projects
Reproducibility of Results
Vital Capacity
English
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Patients present loss of lung function, dyspnea and dry cough. Diagnosis requires compatible radiologic imaging and, in undetermined cases, invasive procedures such as bronchoscopy and surgical lung biopsy. The pathophysiological mechanisms of IPF are not completely understood. Lung injury with abnormal alveolar epithelial repair is thought to be a major cause for activation of profibrotic pathways in IPF. Metabolic signatures might indicate pathological pathways involved in disease development and progression. Reliable serum biomarker would help to improve both diagnostic approach and monitoring of drug effects.
METHOD
The global metabolic profiles measured by ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) of ten stable IPF patients were compared to the ones of ten healthy participants. The results were validated in an additional study of eleven IPF patients and ten healthy controls.
RESULTS
We discovered 10 discriminative metabolic features using multivariate and univariate statistical analysis. Among them, we identified one metabolite at a retention time of 9.59 min that was two times more abundant in the serum of IPF patients compared to healthy participants. Based on its ion pattern, a lysophosphatidylcholine (LysoPC) was proposed. LysoPC is a precursor of lysophosphatidic acid (LPA) - a known mediator for lung fibrosis with its pathway currently being evaluated as new therapeutic drug target for IPF and other fibrotic diseases.
CONCLUSIONS
We identified a LysoPC by UHPLC-HRMS as potential biomarker in serum of patients with IPF. Further validation studies in a larger cohort are necessary to determine its role in IPF.
TRIAL REGISTRATION
Serum samples from IPF patients have been obtained within the clinical trial NCT02173145 at baseline and from the idiopathic interstitial pneumonia (IIP) cohort study. The study was approved by the Swiss Ethics Committee, Bern (KEK 002/14 and 246/15 or PB_2016-01524).
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Patients present loss of lung function, dyspnea and dry cough. Diagnosis requires compatible radiologic imaging and, in undetermined cases, invasive procedures such as bronchoscopy and surgical lung biopsy. The pathophysiological mechanisms of IPF are not completely understood. Lung injury with abnormal alveolar epithelial repair is thought to be a major cause for activation of profibrotic pathways in IPF. Metabolic signatures might indicate pathological pathways involved in disease development and progression. Reliable serum biomarker would help to improve both diagnostic approach and monitoring of drug effects.
METHOD
The global metabolic profiles measured by ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) of ten stable IPF patients were compared to the ones of ten healthy participants. The results were validated in an additional study of eleven IPF patients and ten healthy controls.
RESULTS
We discovered 10 discriminative metabolic features using multivariate and univariate statistical analysis. Among them, we identified one metabolite at a retention time of 9.59 min that was two times more abundant in the serum of IPF patients compared to healthy participants. Based on its ion pattern, a lysophosphatidylcholine (LysoPC) was proposed. LysoPC is a precursor of lysophosphatidic acid (LPA) - a known mediator for lung fibrosis with its pathway currently being evaluated as new therapeutic drug target for IPF and other fibrotic diseases.
CONCLUSIONS
We identified a LysoPC by UHPLC-HRMS as potential biomarker in serum of patients with IPF. Further validation studies in a larger cohort are necessary to determine its role in IPF.
TRIAL REGISTRATION
Serum samples from IPF patients have been obtained within the clinical trial NCT02173145 at baseline and from the idiopathic interstitial pneumonia (IIP) cohort study. The study was approved by the Swiss Ethics Committee, Bern (KEK 002/14 and 246/15 or PB_2016-01524).
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s12931-018-0714-2
- PMID 29321022
- Persistent URL
- https://sonar.ch/global/documents/201440
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