CYFRA 21-1 Predicts Progression in Idiopathic Pulmonary Fibrosis: A Prospective Longitudinal Analysis of the PROFILE Cohort.

Molyneaux, PL; Fahy, WA; Byrne, AJ; Braybrooke, R; Saunders, P; Toshner, R; Albers, G; Chua, F; Renzoni, EA; Wells, AU; Karkera, Y; Oballa, E; Saini, G; Nicholson, AG; Jenkins, RG; Maher, TM

CYFRA 21-1 Predicts Progression in Idiopathic Pulmonary Fibrosis: A Prospective Longitudinal Analysis of the PROFILE Cohort.

Molyneaux, PL Fahy, WA Byrne, AJ Braybrooke, R Saunders, P Toshner, R Albers, G

Chua, F Renzoni, EA Wells, AU Karkera, Y Oballa, E Saini, G Nicholson, AG Jenkins, RG Maher, TM

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Publisher:: American Thoracic Society
Publication Type:: Journal Article
Citation:: Am J Respir Crit Care Med, 2022, 205, (12), pp. 1440-1448
Issue Date:: 2022-06-15

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Field	Value	Language
dc.contributor.author	Molyneaux, PL
dc.contributor.author	Fahy, WA
dc.contributor.author	Byrne, AJ
dc.contributor.author	Braybrooke, R
dc.contributor.author	Saunders, P
dc.contributor.author	Toshner, R
dc.contributor.author	Albers, G https://orcid.org/0000-0002-8249-6956
dc.contributor.author	Chua, F
dc.contributor.author	Renzoni, EA
dc.contributor.author	Wells, AU
dc.contributor.author	Karkera, Y
dc.contributor.author	Oballa, E
dc.contributor.author	Saini, G
dc.contributor.author	Nicholson, AG
dc.contributor.author	Jenkins, RG
dc.contributor.author	Maher, TM
dc.date.accessioned	2023-07-24T22:17:05Z
dc.date.available	2023-07-24T22:17:05Z
dc.date.issued	2022-06-15
dc.identifier.citation	Am J Respir Crit Care Med, 2022, 205, (12), pp. 1440-1448
dc.identifier.issn	1073-449X
dc.identifier.issn	1535-4970
dc.identifier.uri	http://hdl.handle.net/10453/171633
dc.description.abstract	Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal condition for which there are a lack of effective biomarkers to guide therapeutic decision making. Objectives: To determine the relationship between serum concentrations of the cytokeratin fragment CYFRA 21-1 and disease progression and mortality in individuals with IPF enrolled in the Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE) study. Methods: CYFRA 21-1 was identified by immunohistochemistry in samples of human lung obtained at surgery. Concentrations of CYFRA 21-1 were measured using an ELISA-based assay in serum samples collected at baseline, 1 month, and 3 months from 491 individuals with an incident diagnosis of IPF who were enrolled in the PROFILE study and from 100 control subjects at baseline. Study subjects were followed for a minimum of 3 years after their first blood draw. Measurements and Main Results: CYFRA 21-1 localizes to hyperplastic epithelium in IPF lung tissue. Peripheral CYFRA 21-1 concentrations were significantly higher in subjects with IPF than in healthy control subjects in both the discovery (n = 132) (control: 0.96 ± 0.81 ng/ml; vs. IPF: 2.34 ± 2.15 ng/ml; P < 0.0001) and validation (n = 359) (control: 2.21 ± 1.54 ng/ml; and IPF: 4.13 ± 2.77 ng/ml; P < 0.0001) cohorts. Baseline concentrations of CYFRA 21-1 were able to distinguish individuals at risk of 12-month disease progression (C-statistic, 0.70; 95% confidence interval, 0.61-0.79; P < 0.0001) and were predictive of overall mortality (hazard ratio, 1.12 [95% confidence interval, 1.06-1.19] per 1 ng/ml increase in CYFRA 21-1; P = 0.0001). Furthermore, 3-month change in concentrations of CYFRA 21-1 separately predicted 12-month and overall survival in both the discovery and validation cohorts. Conclusions: CYFRA 21-1, a marker of epithelial damage and turnover, has the potential to be an important prognostic and therapeutic biomarker in individuals with IPF.
dc.format	Print
dc.language	eng
dc.publisher	American Thoracic Society
dc.relation.ispartof	Am J Respir Crit Care Med
dc.relation.isbasedon	10.1164/rccm.202107-1769OC
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	Respiratory System
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.subject.classification	3202 Clinical sciences
dc.subject.mesh	Antigens, Neoplasm
dc.subject.mesh	Biomarkers
dc.subject.mesh	Disease Progression
dc.subject.mesh	Humans
dc.subject.mesh	Idiopathic Pulmonary Fibrosis
dc.subject.mesh	Keratin-19
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Humans
dc.subject.mesh	Disease Progression
dc.subject.mesh	Antigens, Neoplasm
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Keratin-19
dc.subject.mesh	Idiopathic Pulmonary Fibrosis
dc.subject.mesh	Biomarkers
dc.subject.mesh	Antigens, Neoplasm
dc.subject.mesh	Biomarkers
dc.subject.mesh	Disease Progression
dc.subject.mesh	Humans
dc.subject.mesh	Idiopathic Pulmonary Fibrosis
dc.subject.mesh	Keratin-19
dc.subject.mesh	Prospective Studies
dc.title	CYFRA 21-1 Predicts Progression in Idiopathic Pulmonary Fibrosis: A Prospective Longitudinal Analysis of the PROFILE Cohort.
dc.type	Journal Article
utslib.citation.volume	205
utslib.location.activity	United States
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
dc.date.updated	2023-07-24T22:17:01Z
pubs.issue	12
pubs.publication-status	Published
pubs.volume	205
utslib.citation.issue	12

Abstract:

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal condition for which there are a lack of effective biomarkers to guide therapeutic decision making. Objectives: To determine the relationship between serum concentrations of the cytokeratin fragment CYFRA 21-1 and disease progression and mortality in individuals with IPF enrolled in the Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE) study. Methods: CYFRA 21-1 was identified by immunohistochemistry in samples of human lung obtained at surgery. Concentrations of CYFRA 21-1 were measured using an ELISA-based assay in serum samples collected at baseline, 1 month, and 3 months from 491 individuals with an incident diagnosis of IPF who were enrolled in the PROFILE study and from 100 control subjects at baseline. Study subjects were followed for a minimum of 3 years after their first blood draw. Measurements and Main Results: CYFRA 21-1 localizes to hyperplastic epithelium in IPF lung tissue. Peripheral CYFRA 21-1 concentrations were significantly higher in subjects with IPF than in healthy control subjects in both the discovery (n = 132) (control: 0.96 ± 0.81 ng/ml; vs. IPF: 2.34 ± 2.15 ng/ml; P < 0.0001) and validation (n = 359) (control: 2.21 ± 1.54 ng/ml; and IPF: 4.13 ± 2.77 ng/ml; P < 0.0001) cohorts. Baseline concentrations of CYFRA 21-1 were able to distinguish individuals at risk of 12-month disease progression (C-statistic, 0.70; 95% confidence interval, 0.61-0.79; P < 0.0001) and were predictive of overall mortality (hazard ratio, 1.12 [95% confidence interval, 1.06-1.19] per 1 ng/ml increase in CYFRA 21-1; P = 0.0001). Furthermore, 3-month change in concentrations of CYFRA 21-1 separately predicted 12-month and overall survival in both the discovery and validation cohorts. Conclusions: CYFRA 21-1, a marker of epithelial damage and turnover, has the potential to be an important prognostic and therapeutic biomarker in individuals with IPF.

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http://hdl.handle.net/10453/171633