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Cited by 273Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisOccupational and environmental lung diseasesChronic Obstructive Pulmonary Disease (COPD) Research

An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study

Open access
Maher, Toby M, Oballa, Eunice, Simpson, Juliet K, Porte, Joanne, Habgood, Anthony, Fahy, William A, Flynn, Aiden, Molyneaux, Philip L +13 more·2017·The Lancet Respiratory Medicine
DOI 10.1016/s2213-2600(17)30430-7
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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.Methods 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.

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Crossref · 10.1016/s2213-2600(17)30430-7

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  • MMP7 and SP-D were able to distinguish IPF patients from controls and to predict outcome in the PROFILE cohort; baseline SP-D and CA19-9 were higher in progressive versus stable disease, and increasing CA-125 over 3 months was associated with increased mortality.

    “MMP7 and SP-D were able to distinguish IPF patients from controls and to predict outcome in the Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE) cohort (Maher et al., 2017). The same study showed that baseline values of SP-D and the tumour marker CA19-9 were significantly higher in patients with progressive versus stable disease; and increasing concentrations of the”

    From Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies (2023) · cites this paper as Maher et al., 2017

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Authors
Maher, T. M., Oballa, E., Simpson, J. K., Porte, J., Habgood, A., Fahy, W. A., Flynn, A., Molyneaux, P. L., Braybrooke, R., Divyateja, H., Parfrey, H., Rassl, D., Russell, A.-M., Saini, G., Renzoni, E. A., Duggan, A.-M., Hubbard, R., Wells, A. U., Lukey, P. T., Marshall, R. P., & Jenkins, R. G.
Affiliations
  • National Institute for Health and Care Research (GB)
  • GlaxoSmithKline (United Kingdom) (GB)
  • Nottingham University Hospitals NHS Trust (GB)
  • University of Nottingham (GB)
  • Royal Papworth Hospital (GB)
ORCID
Venue
The Lancet Respiratory Medicine
Publisher
Elsevier BV
Published
2017-12
Volume
5
Issue
12
Pages
946-955
ISSN
2213-2600 (ISSN-L)
DOI
10.1016/s2213-2600(17)30430-7
OpenAlex
W2770778260
Cited by
271
References
34
Citations by year
2026: 21 · 2025: 28 · 2024: 39 · 2023: 37 · 2022: 33 · 2021: 36 · 2020: 36 · 2019: 26 · 2018: 14 · 2017: 1
FWCI
17.28
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Respiratory Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Repository@Nottingham (University of Nottingham) (acceptedVersion, other-oa)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
  • Nottingham ePrints (University of Nottingham) (submittedVersion, cc-by)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institute for Health and Care Research (PB-PG-0712-28073, CS-2013-13-017, CDRF-2012-03-053)
  • Versus Arthritis (20719)
  • Medical Research Council (MR/N005953/1)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
Keywords
idiopathic pulmonary fibrosis, serum biomarkers, surfactant protein D, CA19-9, CA125, matrix metalloproteinase-7, disease progression prediction, mortality risk, epithelial damage, multiplex immunoassay, treatment-naive patients, lung histology, metaplastic epithelium, biomarker discovery
MeSH terms
Enzyme-Linked Immunosorbent Assay, Epithelium, Female, Humans, Longitudinal Studies, Lung, Male, Predictive Value of Tests, Prospective Studies, Biomarkers, Case-Control Studies, CA-125 Antigen, CA-19-9 Antigen, Disease Progression, Matrix Metalloproteinase 7, Pulmonary Surfactant-Associated Protein D, Idiopathic Pulmonary Fibrosis

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