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Relationship between gene expression and lung function in Idiopathic Interstitial Pneumonias
Mark P Steele1, Leah G Luna2, Christopher D Coldren3
1Department of Medicine, Vanderbilt University, Nashville, TN, USA.
BMC Genomics
|October 28, 2015
Summary
Gene expression in idiopathic interstitial pneumonia (IIP) lung tissue correlates with lung function. These findings offer potential biomarkers and therapeutic targets for IIP severity, improving patient prognoses.
Area of Science:
- Pulmonary Medicine
- Genomics
- Molecular Biology
Background:
- Idiopathic interstitial pneumonias (IIPs) are progressive lung scarring diseases.
- Lung function is critical for survival in IIPs.
- Transcriptional profiles may enhance IIP prognostic approaches.
Purpose of the Study:
- To identify gene expression patterns in IIP lung tissue associated with lung function.
- To explore potential biomarkers and therapeutic targets for IIP severity.
Main Methods:
- Gene expression profiling of 167 IIP lung tissue specimens and 50 controls.
- Analysis of gene expression associated with lung function measures (FVC, DLCO).
- Validation in an independent cohort of 131 IIPs and 40 controls.
Main Results:
- Identified 58 transcripts associated with mild vs. severe IIP disease.
- Discovered novel candidate genes (RTKN2, PI15) and established fibrosis genes.
- Protein-protein interactome analysis revealed increased cell cycle, apoptosis, hypoxia, and dampened immunity in severe IIPs.
Conclusions:
- Commonalities and differences in gene expression exist across IIP subtypes.
- Disease progression significantly alters expression of novel and established IIP-related genes and pathways.
- Identified genes and pathways are promising candidates for IIP biomarker and therapeutic development.
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