An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess potential biomarkers to predict outcomes for people with IPF. METHOD: PROFILE is a large prospective longitudinal cohort of treatment-naive patients with IPF. We adopted a two-stage discovery and validation design using patients from the PROFILE cohort. For the discovery analysis, we examined 106 patients and 50 age and sex matched healthy controls from Nottingham University Hospitals NHS Trust and the Royal Brompton Hospital. We did an unbiased, multiplex immunoassay assessment of 123 biomarkers. We further investigated promising novel markers by immunohistochemical assessment of IPF lung tissue. In the validation analysis, we examined samples from 206 people with IPF from among the remaining 212 patients recruited to PROFILE Central England. We used the samples to attempt to replicate the biomarkers identified from the discovery analysis by use of independent immunoassays for each biomarker. We investigated the predictive power of the selected biomarkers to identify individuals with IPF who were at risk of progression or death. The PROFILE studies are registered on ClinicalTrials.gov, numbers NCT01134822 (PROFILE Central England) and NCT01110694 (PROFILE Royal Brompton Hospital). FINDINGS: In the discovery analysis, we identified four serum biomarkers (surfactant protein D, matrix metalloproteinase 7, CA19-9, and CA-125) that were suitable for replication. Histological assessment of CA19-9 and CA-125 suggested that these proteins were markers of epithelial damage. Replication analysis showed that baseline values of surfactant protein D (46·6 ng/mL vs 34·6 ng/mL, p=0·0018) and CA19-9 (53·7 U/mL vs 22·2 U/mL; p<0·0001) were significantly higher in patients with progressive disease than in patients with stable disease, and rising concentrations of CA-125 over 3 months were associated with increased risk of mortality (HR 2·542, 95% CI 1·493-4·328, p=0·00059). INTERPRETATION: We have identified serum proteins secreted from metaplastic epithelium that can be used to predict disease progression and death in IPF. FUNDING: GlaxoSmithKline R&D and the UK Medical Research Council.
Date Issued
2017-12-01
Date Acceptance
2017-10-04
Citation
Lancet Respiratory Medicine, 2017, 5 (12), pp.946-955
ISSN
2213-2600
Publisher
Elsevier
Start Page
946
End Page
955
Journal / Book Title
Lancet Respiratory Medicine
Volume
5
Issue
12
Copyright Statement
© 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
National Institute for Health Research
British Lung Foundation
Versus Arthritis
Identifier
PII: S2213-2600(17)30430-7
Grant Number
CS-2013-13-017
C17-3
20719
Subjects
Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
INTERSTITIAL LUNG-DISEASE
TUMOR-MARKERS
PROTEIN-D
CANCER
NINTEDANIB
MUC16
PATHOGENESIS
PIRFENIDONE
ASSOCIATION
GALECTIN-3
Biomarkers
CA-125 Antigen
CA-19-9 Antigen
Case-Control Studies
Disease Progression
Enzyme-Linked Immunosorbent Assay
Epithelium
Female
Humans
Idiopathic Pulmonary Fibrosis
Longitudinal Studies
Lung
Male
Matrix Metalloproteinase 7
Predictive Value of Tests
Prospective Studies
Pulmonary Surfactant-Associated Protein D
Lung
Epithelium
Humans
Disease Progression
Pulmonary Surfactant-Associated Protein D
CA-19-9 Antigen
CA-125 Antigen
Enzyme-Linked Immunosorbent Assay
Case-Control Studies
Longitudinal Studies
Prospective Studies
Predictive Value of Tests
Female
Male
Matrix Metalloproteinase 7
Idiopathic Pulmonary Fibrosis
Biomarkers
1103 Clinical Sciences
1117 Public Health and Health Services
1199 Other Medical and Health Sciences
Publication Status
Published
Date Publish Online
2017-11-14