Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression

Ilse M Boudewijn,Frank Van Den Elshout,Khaled Mansour,Alen Faiz,Wim Timens,Nick H T Ten Hacken,Henk Pasma ,Dirkje S Postma,Pascal Wielders,Huib A M Kerstjens,Marc E Lenburg,Corry‐Anke Brandsma ,Irene H Heijink,Harold G De Bruin,Avrum Spira,Susan Hoonhorst ,Marnix R Jonker ,J Sebastiaan Vroegop,Wim Boersma ,Eef D Telenga,Katrina Steiling,Victor Guryev,Erica Van Der Wiel,Maarten Van Den Berge

doi:10.1186/s12931-017-0696-5

Abstract

BackgroundNasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium.MethodsGenome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls.ResultsIn nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001).ConclusionWe identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD.Trial registrationClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008).

Highlights

Nasal gene expression profiling is a promising method to characterize Chronic obstructive pulmonary disease (COPD) non-invasively
COPD-associated genes in nasal epithelium Nasal epithelial gene expression levels of 135 genes were significantly altered in individuals with COPD versus controls (FDR
We found that out of 135 genes associated with COPD in nasal epithelium, 28 genes (21%) overlapped with genes associated with COPD in bronchial epithelium in similar direction (FDR 0.01), which is in line with the results of Obeidat et al there are some considerable differences between the studies

Summary

Introduction

Nasal gene expression profiling is a promising method to characterize COPD non-invasively. COPD is currently the fourth leading cause of death worldwide, according to the World Health Organization [2] Some genetic factors, such as alpha-1 anti-trypsin deficiency, and environmental exposures, such as cigarette smoking, are well-established contributors to COPD, yet the precise molecular mechanisms of the disease remain to be elucidated. We have previously demonstrated that the bronchial airway epithelium responds to cigarette smoke exposure with characteristic alterations in gene expression [3] Building upon this observation, we identified a bronchial airway gene expression signature associated with COPD and disease severity that is altered in COPD-affected lung tissue [4]. We identified a bronchial airway gene expression signature associated with COPD and disease severity that is altered in COPD-affected lung tissue [4] These data suggest that bronchial gene expression obtained by bronchoscopy may be applied to monitor disease activity in COPD. Nasal epithelial gene expression profiling could potentially function as a non-invasive biomarker in COPD

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