title: Expression profiling identifies genes involved in emphysema severity.
abstract: Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients.Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.Class comparison identified 98 differentially expressed genes (p < 0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity.Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3.
authors.affiliation: Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia. ss.francis@uqconnect.edu.au
authors.forename: Santiyagu M Savarimuthu
authors.initials: SM
authors.lastname: Francis
authors.forename: Jill E
authors.initials: JE
authors.lastname: Larsen
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Pavey
authors.forename: Rayleen V
authors.initials: RV
authors.lastname: Bowman
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Kwun M
authors.initials: KM
authors.lastname: Fong
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis*; D011656:Pulmonary Emphysema / Q000175:diagnosis* / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D011506:Proteins