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

Respiratory Research

Research

Pascal Wielders¹  Marc E. Lenburg²  Katrina Steiling²  Avrum Spira²  Victor Guryev³  J. Sebastiaan Vroegop⁴  Henk R. Pasma⁵  Wim G. Boersma⁶  Khaled Mansour⁷  Frank van den Elshout⁸  Marnix R. Jonker⁹  Harold G. de Bruin⁹  Eef D. Telenga^1,10  Susan J. M. Hoonhorst^1,10  Huib A. M. Kerstjens^1,10  Ilse M. Boudewijn^1,10  Dirkje S. Postma^1,10  Maarten van den Berge^1,10  Nick H. T. ten Hacken^1,10  Erica van der Wiel^1,10  Alen Faiz^1,10  Irene H. Heijink^1,11  Wim Timens^1,12  Corry-Anke Brandsma^1,12 

[1] Catharina Hospital, Department of Pulmonary Diseases, Eindhoven, the Netherlands;Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA, USA;Bioinformatics Program, Boston University, Boston, MA, USA;European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands;Martini Hospital, Department of Pulmonary Diseases, Groningen, the Netherlands;Medical Center Leeuwarden, Department of Pulmonary Diseases, Leeuwarden, the Netherlands;Noordwest Ziekenhuisgroep, Department of Pulmonary Diseases, Alkmaar, the Netherlands;Orbis Concern, Department of Pulmonary Diseases, Sittard, the Netherlands;Rijnstate Hospital, Department of Pulmonary Diseases, Arnhem, the Netherlands;University of Groningen, University Medical Center Groningen, Department of Pathology, section Medical Biology, Groningen, the Netherlands;University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands;University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands;University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands;University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands;University of Groningen, University Medical Center Groningen, Department of Pathology, section Medical Biology, Groningen, the Netherlands;University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands;University of Groningen, University Medical Center Groningen, Department of Pathology, section Medical Biology, Groningen, the Netherlands;

关键词: COPD;    Nasal epithelium;    Bronchial epithelium;    Genome wide gene expression;    Microarray;   

DOI  :  10.1186/s12931-017-0696-5

 received in 2017-08-30, accepted in 2017-12-11,  发布年份 2017

来源: Springer

【 摘 要 】

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).

【 授权许可】

CC BY   
© The Author(s). 2017