Abstract
Idiopathic pulmonary fibrosis (IPF) is a lung parenchymal disease of unknown cause usually occurring in older adults. It is a chronic and progressive condition with poor prognosis and diagnosis is largely clinical. Currently, there exist few biomarkers that can predict patient outcome or response to therapies. Together with lack of markers, the need for novel markers for the detection and monitoring of IPF, is paramount. We have performed label-free plasma proteomics of thirty six individuals, 17 of which had confirmed IPF. Proteomics data was analyzed by volcano plot, hierarchical clustering, Partial-least square discriminant analysis (PLS-DA) and Ingenuity pathway analysis. Univariate and multivariate statistical analysis overlap identified haptoglobin-related protein as a possible marker of IPF when compared to control samples (Area under the curve 0.851, ROC-analysis). LXR/RXR activation and complement activation pathways were enriched in t-test significant proteins and oxidative regulators, complement proteins and protease inhibitors were enriched in PLS-DA significant proteins. Our pilot study points towards aberrations in complement activation and oxidative damage in IPF patients and provides haptoglobin-related protein as a new candidate biomarker of IPF.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a lung parenchymal disease of unknown cause usually occurring in older adults
Idiopathic pulmonary fibrosis is chronic, progressive, interstitial pneumonia of unknown cause usually occurring in older adults and presents with usual interstitial pneumonia (UIP) in histopathological and/or radiological findings
The median time for diagnosis of IPF from symptom onset is 12 months and a quarter of the patients are not diagnosed for up to 26 months[7]. This is unfortunate as the median survival time of patients with IPF ranges from 30–42 months[8,9]
Summary
Idiopathic pulmonary fibrosis (IPF) is a lung parenchymal disease of unknown cause usually occurring in older adults. It is a chronic and progressive condition with poor prognosis and diagnosis is largely clinical. Idiopathic pulmonary fibrosis is chronic, progressive, interstitial pneumonia of unknown cause usually occurring in older adults and presents with usual interstitial pneumonia (UIP) in histopathological and/or radiological findings. We have performed label-free plasma proteomics on 36 plasma samples including 17 confirmed IPF cases (2011 ATS/ERS/JRS/ALAT diagnostic guidelines2) and 19 healthy controls. Multivariate statistical analysis methods were employed to find suitable high-confidence biomarkers Their performance was evaluated by ROC curve analysis
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