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| Status |
Public on Jun 20, 2012 |
| Title |
Modulation of Cystatin A Expression in Human Airway Epithelium Related to Genotype, Smoking COPD and Lung Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
SNP genotyping by SNP array
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| Summary |
Cystatin A (gene: CSTA), is up-regulated in non-small-cell lung cancer (NSCLC) and dysplastic vs normal human bronchial epithelium. In the context that chronic obstructive pulmonary disease (COPD), a small airway epithelium (SAE) disorder, is independently associated with NSCLC (especially squamous cell carcinoma, SCC), but only occurs in a subset of smokers, we hypothesized that genetic variation, smoking and COPD modulate CSTA gene expression levels in SAE, with further up-regulation in SCC. Gene expression was assessed by microarray in SAE of 178 individuals [healthy nonsmokers (n=60), healthy smokers (n=82), and COPD smokers (n=36)], with corresponding large airway epithelium (LAE) data in a subset (n=52). Blood DNA was genotyped by SNP microarray. Twelve SNPs upstream of the CSTA gene were all significantly associated with CSTA SAE gene expression (p<0.04 to 5 x 10-4). CSTA gene expression levels in SAE were higher in COPD smokers (28.4 ± 2.0) than healthy smokers (19.9 ± 1.4, p<10-3), who in turn had higher levels than nonsmokers (16.1 ± 1.1, p<0.04). CSTA LAE gene expression was also smoking-responsive (p<10-3). Using comparable publicly available NSCLC expression data, CSTA was up-regulated in SCC vs LAE (p<10-2) and down-regulated in adenocarcinoma vs SAE (p<10-7). All phenotypes were associated with significantly different proportional gene expression of CSTA to cathepsins. The data demonstrate that regulation of CSTA expression in human airway epithelium is influenced by genetic variability, smoking, and COPD, and is further up-regulated in SCC, all of which should be taken into account when considering the role of CSTA in NSCLC pathogenesis.
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| Overall design |
CSTA gene expression was assessed in the small airway epithelium obtained by bronchoscopy from 178 individuals, including healthy nonsmokers (n= 60) and healthy smokers (n= 118) and the large airway epithelium from healthy nonsmokers (n=21) and healthy smokers(n=31).
*** Processed data not provided for all gene expression records. ***
Blood DNA from the majority of these individuals was genotyped and an association analysis of gene expression with genotypes of all 48 SNPs within 100 kb of CSTA was performed in PLINK, and tested for significance following 103 permutations within ancestral clusters.
Supplementary file (linked below) reports genotypes of all 48 SNPs within 100 kb of the CSTA gene for the 112 genotyping Samples.
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| Contributor(s) |
Butler MW, Fukui T, Salit J, Shaykhiev R, Mezey J, Hackett NR, Crystal RG |
| Citation(s) |
21325429 |
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| Submission date |
May 28, 2010 |
| Last update date |
Jul 08, 2019 |
| Contact name |
Yael Strulovici-Barel |
| E-mail(s) |
yas2003@med.cornell.edu
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| Organization name |
Weill Cornell Medical College
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| Department |
Department of Genetic Medicine
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| Lab |
Crystal
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| Street address |
1300 York Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (2) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
| GPL6804 |
[GenomeWideSNP_5] Affymetrix Genome-Wide Human SNP 5.0 Array |
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| Samples (342)
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| Relations |
| BioProject |
PRJNA128993 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22047_RAW.tar |
6.5 Gb |
(http)(custom) |
TAR (of CEL, CHP) |
| GSE22047_SNP_data.txt.gz |
2.3 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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