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Respir Res. 2017 Dec 21;18(1):213. doi: 10.1186/s12931-017-0696-5.

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

Author information

1
University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands. i.m.boudewijn@umcg.nl.
2
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands. i.m.boudewijn@umcg.nl.
3
University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands.
4
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands.
5
Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA, USA.
6
Bioinformatics Program, Boston University, Boston, MA, USA.
7
University of Groningen, University Medical Center Groningen, Department of Pathology, section Medical Biology, Groningen, the Netherlands.
8
Martini Hospital, Department of Pulmonary Diseases, Groningen, the Netherlands.
9
Medical Center Leeuwarden, Department of Pulmonary Diseases, Leeuwarden, the Netherlands.
10
Noordwest Ziekenhuisgroep, Department of Pulmonary Diseases, Alkmaar, the Netherlands.
11
Catharina Hospital, Department of Pulmonary Diseases, Eindhoven, the Netherlands.
12
Rijnstate Hospital, Department of Pulmonary Diseases, Arnhem, the Netherlands.
13
Orbis Concern, Department of Pulmonary Diseases, Sittard, the Netherlands.
14
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Abstract

BACKGROUND:

Nasal 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.

METHODS:

Genome 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.

RESULTS:

In 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).

CONCLUSION:

We 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 REGISTRATION:

ClinicalTrials.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).

KEYWORDS:

Bronchial epithelium; COPD; Genome wide gene expression; Microarray; Nasal epithelium

PMID:
29268739
PMCID:
PMC5740586
DOI:
10.1186/s12931-017-0696-5
[Indexed for MEDLINE]
Free PMC Article

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