Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Methylation profiles of COPD small airways

ABSTRACT: Rationale: DNA methylation is an epigenetic modification that is highly disrupted in response to cigarette smoke and involved in a wide spectrum of malignant and non-malignant diseases, but surprisingly not previously assessed in small airways of patients with chronic obstructive pulmonary disease (COPD). Small airways are the primary sites of airflow obstruction in COPD. We sought to determine whether DNA methylation patterns are disrupted in small airway epithelia of COPD patients, and evaluate whether changes in gene expression are associated with these disruptions. Methods: Genome-wide methylation and gene expression analysis were performed on small airway epithelial DNA and RNA obtained from the same patient during bronchoscopy, using Illumina's Infinium HM27 and Affymetrix's Genechip Human Gene 1.0 ST arrays. To control for known effects of cigarette smoking on DNA methylation, methylation and gene expression profiles were compared between former smokers (FS) with and without COPD matched for age, pack years and years of smoking cessation. Results: Our results indicate that aberrant DNA methylation is i) a genome-wide phenomenon in small airways of patients with COPD and ii) associated with altered expression of genes and pathways important to COPD, such as the Nrf2 oxidative response pathway. Conclusions: DNA methylation is likely an important mechanism contributing to modulation of genes important to COPD pathology. Since these methylation events may underlie disease-specific gene-expression changes, their characterization is a critical first step towards the development of epigenetic markers and an opportunity for developing novel epigenetic therapeutic interventions for COPD. Bisulphite converted DNA from small airway (airways less than <2 mm in diameter) from 38 former smokers: 15 subjects with COPD (post bronchodilator FEV1/FVC ratio <70% and FEV1 predicted M-bM-^IM-$ 80%) and 21 with normal lung function, were hybridized to the Illumina Infinium 27k Human Methylation Beadchip.

ORGANISM(S): Homo sapiens

SUBMITTER: Wan Lam

PROVIDER: E-GEOD-55454 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

DNA methylation is globally disrupted and associated with expression changes in chronic obstructive pulmonary disease small airways.

Vucic Emily A EA Chari Raj R Thu Kelsie L KL Wilson Ian M IM Cotton Allison M AM Kennett Jennifer Y JY Zhang May M Lonergan Kim M KM Steiling Katrina K Brown Carolyn J CJ McWilliams Annette A Ohtani Keishi K Lenburg Marc E ME Sin Don D DD Spira Avrum A Macaulay Calum E CE Lam Stephen S Lam Wan L WL

American journal of respiratory cell and molecular biology 20140501 5

DNA methylation is an epigenetic modification that is highly disrupted in response to cigarette smoke and involved in a wide spectrum of malignant and nonmalignant diseases, but surprisingly not previously assessed in small airways of patients with chronic obstructive pulmonary disease (COPD). Small airways are the primary sites of airflow obstruction in COPD. We sought to determine whether DNA methylation patterns are disrupted in small airway epithelia of patients with COPD, and evaluate wheth ...[more]

PMID: 24298892

Similar Datasets

Project description:Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers; The microarray data deposited here is from 11 HG-U133A GeneChips, from 5 normal non-smokers and 6 phenotypic normal smokers, large airways. Samples from the small airways of these individuals have been obtained and analyzed using the HG-U133A GeneChip; the small airway samples are in GEO Accession Number GSE 3320, and the data analysis is described in Harvey, B-G; Heguy, A.; Leopold, P.L.; Carolan, B.; Ferris, B. and Crystal R.G. Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking. J. Mol. Med (in press). These data are part of a study aimed at understanding how cigarette smoking modifies neuroendocrine cells, in which microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals (normal nonsmokers, normal smokers, smokers with early COPD and smokers with established COPD). Of 11 genes considered to be neuroendocrine cell-specific, only ubiquitin C-terminal hydrolase L1(UCHL1), a member of the ubiquitin proteasome pathway, was consistently upregulated in smokers compared to nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemistry of bronchial biopsies of smokers compared to nonsmokers. Interestingly, however, while UCHL1 expression was present only in neuroendocrine cells of the airway epithelium in nonsmokers, UCHL1 expression was also expressed in ciliated epithelial cells in smokers, an intriguing observation in light of recent observations that ciliated cells can are capable of transdifferentiating to other airway epithelium. In the context that UCHL1 is involved in the degradation of unwanted, misfolded or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy. Experiment Overall Design: comparison of gene expression in airway epithelial cells of the large airways of phenotypic normal smokers vs normal non-smokers

Project description:Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers The microarray data deposited here is from 39 HG-U133 Plus 2.0 GeneChips, from 12 normal non-smokers, 12 phenotypic normal smokers, 9 Early COPD and 6 COPD individuals, all small airways, all small airway. A subset of these samples have been already submitted under GEO Accession Number GSE 4498. These are: 12 non-smokers samples (GSM101095-GSM101106) and 10 smoker samples (GSM101107-GSM101116). These 22 samples that are also in GSE4498 were described in Harvey, B-G; Heguy, A.; Leopold, P.L.; Carolan, B.; Ferris, B. and Crystal R.G. Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking. J. Mol. Med (in press). These data are part of a study aimed at understanding how cigarette smoking modifies neuroendocrine cells, in which microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals (normal nonsmokers, normal smokers, smokers with early COPD and smokers with established COPD). Of 11 genes considered to be neuroendocrine cell-specific, only ubiquitin C-terminal hydrolase L1(UCHL1), a member of the ubiquitin proteasome pathway, was consistently upregulated in smokers compared to nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemistry of bronchial biopsies of smokers compared to nonsmokers. Interestingly, however, while UCHL1 expression was present only in neuroendocrine cells of the airway epithelium in nonsmokers, UCHL1 expression was also expressed in ciliated epithelial cells in smokers, an intriguing observation in light of recent observations that ciliated cells can are capable of transdifferentiating to other airway epithelium. In the context that UCHL1 is involved in the degradation of unwanted, misfolded or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy. Keywords: non-smokers vs phenotypic normal smokers, smokers with early COPD, and smokers with COPD

Dataset Information

Methylation profiles of COPD small airways

Publications

DNA methylation is globally disrupted and associated with expression changes in chronic obstructive pulmonary disease small airways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets