Imperial College London
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ProfessorPhilipMolyneaux

Faculty of Medicine, National Heart & Lung Institute

Professor of Interstitial Lung Disease
 
 
 
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p.molyneaux

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Herazo-Maya:2017:10.1016/S2213-2600(17)30349-1,
author = {Herazo-Maya, JD and Sun, J and Molyneaux, PL and Li, Q and Villalba, JA and Tzouvelekis, A and Lynn, H and Juan-Guardela, BM and Risquez, C and Osorio, JC and Yan, X and Michel, G and Aurelien, N and Lindell, KO and Klesen, MJ and Moffatt, MF and Cookson, WO and Zhang, Y and Garcia, JGN and Noth, I and Prasse, A and Bar-Joseph, Z and Gibson, KF and Zhao, H and Herzog, EL and Rosas, IO and Maher, TM and Kaminski, N},
doi = {10.1016/S2213-2600(17)30349-1},
journal = {Lancet Respiratory Medicine},
pages = {857--868},
title = {Validation of a 52-gene risk profile for outcome prediction in patients with idiopathic pulmonary fibrosis: an international, multicentre, cohort study},
url = {http://dx.doi.org/10.1016/S2213-2600(17)30349-1},
volume = {5},
year = {2017}
}
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TY  - JOUR
AB  - BACKGROUND: The clinical course of idiopathic pulmonary fibrosis (IPF) is unpredictable. Clinical prediction tools are not accurate enough to predict disease outcomes. METHODS: We enrolled patients with IPF diagnosis in a six-cohort study at Yale University (New Haven, CT, USA), Imperial College London (London, UK), University of Chicago (Chicago, IL, USA), University of Pittsburgh (Pittsburgh, PA, USA), University of Freiburg (Freiburg im Breisgau, Germany), and Brigham and Women's Hospital-Harvard Medical School (Boston, MA, USA). Peripheral blood mononuclear cells or whole blood were collected at baseline from 425 participants and from 98 patients (23%) during 4-6 years' follow-up. A 52-gene signature was measured by the nCounter analysis system in four cohorts and extracted from microarray data (GeneChip) in the other two. We used the Scoring Algorithm for Molecular Subphenotypes (SAMS) to classify patients into low-risk or high-risk groups based on the 52-gene signature. We studied mortality with a competing risk model and transplant-free survival with a Cox proportional hazards model. We analysed timecourse data and response to antifibrotic drugs with linear mixed effect models. FINDINGS: The application of SAMS to the 52-gene signature identified two groups of patients with IPF (low-risk and high-risk), with significant differences in mortality or transplant-free survival in each of the six cohorts (hazard ratio [HR] range 2·03-4·37). Pooled data showed similar results for mortality (HR 2·18, 95% CI 1·53-3·09; p<0·0001) or transplant-free survival (2·04, 1·52-2·74; p<0·0001). Adding 52-gene risk profiles to the Gender, Age, and Physiology index significantly improved its mortality predictive accuracy. Temporal changes in SAMS scores were associated with changes in forced vital capacity (FVC) in two cohorts. Untreated patients did not shift their risk profile over time. A simultaneous
AU  - Herazo-Maya,JD
AU  - Sun,J
AU  - Molyneaux,PL
AU  - Li,Q
AU  - Villalba,JA
AU  - Tzouvelekis,A
AU  - Lynn,H
AU  - Juan-Guardela,BM
AU  - Risquez,C
AU  - Osorio,JC
AU  - Yan,X
AU  - Michel,G
AU  - Aurelien,N
AU  - Lindell,KO
AU  - Klesen,MJ
AU  - Moffatt,MF
AU  - Cookson,WO
AU  - Zhang,Y
AU  - Garcia,JGN
AU  - Noth,I
AU  - Prasse,A
AU  - Bar-Joseph,Z
AU  - Gibson,KF
AU  - Zhao,H
AU  - Herzog,EL
AU  - Rosas,IO
AU  - Maher,TM
AU  - Kaminski,N
DO  - 10.1016/S2213-2600(17)30349-1
EP  - 868
PY  - 2017///
SN  - 2213-2600
SP  - 857
TI  - Validation of a 52-gene risk profile for outcome prediction in patients with idiopathic pulmonary fibrosis: an international, multicentre, cohort study
T2  - Lancet Respiratory Medicine
UR  - http://dx.doi.org/10.1016/S2213-2600(17)30349-1
UR  - http://hdl.handle.net/10044/1/62741
VL  - 5
ER  -
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