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| Status |
Public on Jun 21, 2013 |
| Title |
Molecular phenotyping of the idiopathic interstitial pneumonias [mRNA] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Rationale: The fibrosing idiopathic interstitial pneumonias (IIPs) are classified based on clinical, radiographic, and pathologic criteria. The separation into phenotypic subgroups is useful in predicting outcome and therapeutic strategy; however a large degree of ambiguity remains. Gene expression profiling may contribute to traditional criteria in IIPs by characterizing the dynamic biology that more accurately distinguishes subtypes of these diseases or their prognoses.
Methods: We collected transcriptional and miRNA profiles on lung tissue from 167 subjects with IIP and 50 non-diseased controls. Differential expression of individual transcripts and miRNAs was identified using an ANCOVA model incorporating the clinical diagnosis of each subject as well as age, gender, and smoking status. Validation was performed in an independent cohort of 131 IIPs and 39 non-diseased controls.
Results: Our results demonstrate a substantial degree of overlap in mRNA and miRNA signatures of clinical subtypes of IIP. However, we identify two subtypes of IPF/UIP based on a strong molecular signature associated with expression of cilium genes. We demonstrate that elevated expression of cilium genes is associated with more extensive microscopic honeycombing, more fibroblastic foci, higher expression of the airway mucin gene MUC5B, and better survival in an independent cohort of IPF/UIP patients. Moreover, we identify miRNAs involved in the regulation of cilium-associated gene expression that contribute to novel molecular subphenotypes of IPF.
Conclusions: While subtypes of IIP are related biologically with similar transcriptional profiles, expression of cilium genes appear to identify two unique clinical presentations of IPF/UIP.
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| Overall design |
167 subjects with IIP and 50 non-diseased controls with no replicates
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| Contributor(s) |
Yang IV, Coldren CD, Leach SM, Murphy E, Lin J, Burton R, Groshong S, Cool C, Cosgrove GP, Lynch D, Brown KK, Schwarz MI, Fingerlin TE, Schwartz DA |
| Citation(s) |
23783374 |
| Submission date |
Oct 01, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
David Schwartz |
| E-mail(s) |
DAVID.SCHWARTZ@ucdenver.edu
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| Phone |
303-724-1783
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| Organization name |
University of Colorado, Anschutz Medical Campus
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| Department |
Medicine
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| Street address |
Anschutz Medical Campus
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| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (217)
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| This SubSeries is part of SuperSeries: |
| GSE32539 |
Molecular phenotyping of the idiopathic interstitial pneumonias identifies two Subtypes of idiopathic pulmonary fibrosis. |
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| Relations |
| BioProject |
PRJNA154433 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE32537_RAW.tar |
805.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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