RT Journal Article
SR Electronic
T1 The DNA repair transcriptome in severe COPD
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1701994
DO 10.1183/13993003.01994-2017
VO 52
IS 4
A1 Maor Sauler
A1 Maxime Lamontagne
A1 Eric Finnemore
A1 Jose D. Herazo-Maya
A1 John Tedrow
A1 Xuchen Zhang
A1 Julia E. Morneau
A1 Frank Sciurba
A1 Wim Timens
A1 Peter D. Paré
A1 Patty J. Lee
A1 Naftali Kaminski
A1 Yohan Bossé
A1 Jose L. Gomez
YR 2018
UL http://erj.ersjournals.com/content/52/4/1701994.abstract
AB Inadequate DNA repair is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the mechanisms that underlie inadequate DNA repair in COPD are poorly understood. We applied an integrative genomic approach to identify DNA repair genes and pathways associated with COPD severity.We measured the transcriptomic changes of 419 genes involved in DNA repair and DNA damage tolerance that occur with severe COPD in three independent cohorts (n=1129). Differentially expressed genes were confirmed with RNA sequencing and used for patient clustering. Clinical and genome-wide transcriptomic differences were assessed following cluster identification. We complemented this analysis by performing gene set enrichment analysis, Z-score and weighted gene correlation network analysis to identify transcriptomic patterns of DNA repair pathways associated with clinical measurements of COPD severity.We found 15 genes involved in DNA repair and DNA damage tolerance to be differentially expressed in severe COPD. K-means clustering of COPD cases based on this 15-gene signature identified three patient clusters with significant differences in clinical characteristics and global transcriptomic profiles. Increasing COPD severity was associated with downregulation of the nucleotide excision repair pathway.Systematic analysis of the lung tissue transcriptome of individuals with severe COPD identified DNA repair responses associated with disease severity that may underlie COPD pathogenesis.Severe COPD is associated with reduced transcription of genes involved in the nucleotide excision repair pathway http://ow.ly/TNoa30l9j2y