Lung tissue gene-expression signature for the ageing lung in COPD

De Vries, M; Faiz, A; Woldhuis, RR; Postma, DS; De Jong, TV; Sin, DD; Bossé, Y; Nickle, DC; Guryev, V; Timens, W; Van Den Berge, M; Brandsma, CA

Lung tissue gene-expression signature for the ageing lung in COPD

De Vries, M Faiz, A

Woldhuis, RR

Postma, DS De Jong, TV Sin, DD Bossé, Y Nickle, DC Guryev, V Timens, W Van Den Berge, M Brandsma, CA

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Publication Type:: Journal Article
Citation:: Thorax, 2018, 73 (7), pp. 609 - 617
Issue Date:: 2018-07-01

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Field	Value	Language
dc.contributor.author	De Vries, M	en_US
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538	en_US
dc.contributor.author	Woldhuis, RR https://orcid.org/0000-0001-7516-1034	en_US
dc.contributor.author	Postma, DS	en_US
dc.contributor.author	De Jong, TV	en_US
dc.contributor.author	Sin, DD	en_US
dc.contributor.author	Bossé, Y	en_US
dc.contributor.author	Nickle, DC	en_US
dc.contributor.author	Guryev, V	en_US
dc.contributor.author	Timens, W	en_US
dc.contributor.author	Van Den Berge, M	en_US
dc.contributor.author	Brandsma, CA	en_US
dc.date.available	2017-11-06	en_US
dc.date.issued	2018-07-01	en_US
dc.identifier.citation	Thorax, 2018, 73 (7), pp. 609 - 617	en_US
dc.identifier.issn	0040-6376	en_US
dc.identifier.uri	http://hdl.handle.net/10453/130651
dc.description.abstract	© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Introduction COPD is a chronic, progressive, inflammatory disease of the lungs and the third leading cause of death worldwide. The current knowledge of the pathophysiology of COPD is limited and novel insights in underlying disease mechanisms are urgently needed. Since there are clear parallels between ageing and COPD, we investigated genes underlying lung ageing in general and abnormal lung ageing in COPD. Methods Whole genome mRNA profiling was performed on lung tissue samples (n=1197) and differential gene expression with increasing age was analysed using an adjusted linear regression model. Subsequent pathway analysis was performed using GeneNetwork and the gene-expression signature was compared with lung ageing in the Genotype-Tissue Expression (GTEx) project. In a subset of patients with COPD (n=311) and non-COPD controls (n=270), we performed an interaction analysis between age and COPD to identify genes differentially expressed with age in COPD compared with controls, followed by gene set enrichment pathway analysis. Results We identified a strong gene-expression signature for lung ageing with 3509 differentially expressed genes, of which 33.5% were found nominal significant in the GTEx project. Interestingly, we found EDA2R as a strong candidate gene for lung ageing. The age∗COPD interaction analysis revealed 69 genes significantly differentially expressed with age between COPD and controls. Conclusions Our study indicates that processes related to lung development, cell-cell contacts, calcium signalling and immune responses are involved in lung ageing in general. Pathways related to extracellular matrix, mammalian target of rapamycin signalling, splicing of introns and exons and the ribosome complex are proposed to be involved in abnormal lung ageing in COPD.	en_US
dc.relation.ispartof	Thorax	en_US
dc.relation.isbasedon	10.1136/thoraxjnl-2017-210074	en_US
dc.subject.classification	Respiratory System	en_US
dc.title	Lung tissue gene-expression signature for the ageing lung in COPD	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.citation.volume	73	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
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
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	closed_access
pubs.issue	7	en_US
pubs.publication-status	Published	en_US
pubs.volume	73	en_US

Abstract:

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Introduction COPD is a chronic, progressive, inflammatory disease of the lungs and the third leading cause of death worldwide. The current knowledge of the pathophysiology of COPD is limited and novel insights in underlying disease mechanisms are urgently needed. Since there are clear parallels between ageing and COPD, we investigated genes underlying lung ageing in general and abnormal lung ageing in COPD. Methods Whole genome mRNA profiling was performed on lung tissue samples (n=1197) and differential gene expression with increasing age was analysed using an adjusted linear regression model. Subsequent pathway analysis was performed using GeneNetwork and the gene-expression signature was compared with lung ageing in the Genotype-Tissue Expression (GTEx) project. In a subset of patients with COPD (n=311) and non-COPD controls (n=270), we performed an interaction analysis between age and COPD to identify genes differentially expressed with age in COPD compared with controls, followed by gene set enrichment pathway analysis. Results We identified a strong gene-expression signature for lung ageing with 3509 differentially expressed genes, of which 33.5% were found nominal significant in the GTEx project. Interestingly, we found EDA2R as a strong candidate gene for lung ageing. The age∗COPD interaction analysis revealed 69 genes significantly differentially expressed with age between COPD and controls. Conclusions Our study indicates that processes related to lung development, cell-cell contacts, calcium signalling and immune responses are involved in lung ageing in general. Pathways related to extracellular matrix, mammalian target of rapamycin signalling, splicing of introns and exons and the ribosome complex are proposed to be involved in abnormal lung ageing in COPD.

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http://hdl.handle.net/10453/130651