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Peripheral blood mononuclear cell gene expression in chronic obstructive pulmonary disease
Timothy M Bahr1, Grant J Hughes, Michael Armstrong
1Department of Biostatistics and Informatics, University of Colorado at Denver, Aurora, CO, USA.
American Journal of Respiratory Cell and Molecular Biology
|April 18, 2013
Summary
Distinct molecular signatures in peripheral blood mononuclear cells (PBMCs) differentiate chronic obstructive pulmonary disease (COPD) from smoking alone. These findings reveal potential diagnostic and therapeutic targets for COPD, a systemic inflammatory disease.
Area of Science:
- Pulmonary Medicine
- Genomics
- Biomarker Discovery
Background:
- Most smokers do not develop chronic obstructive pulmonary disease (COPD), suggesting underlying molecular differences.
- Investigating peripheral blood mononuclear cells (PBMCs) may reveal distinct molecular signatures associated with COPD development in smokers.
Purpose of the Study:
- To identify and validate gene expression profiles in PBMCs of current and former smokers with and without COPD.
- To discover novel biomarkers and pathways implicated in COPD pathogenesis.
Main Methods:
- Gene expression profiling using microarrays on 136 subjects from the COPDGene study.
- Multiple linear regression and Ingenuity Pathway Analysis to identify candidate genes and pathways.
- Validation of candidate genes via multiplex quantitative real-time polymerase chain reaction in an independent cohort of 149 subjects.
- Plasma metabolomics to identify biomarkers.
Main Results:
- Differentially expressed pathways in COPD and emphysema subjects involved immune responses, inflammation, and sphingolipid metabolism.
- Twenty-six of 46 candidate genes, including FOXP1, TCF7, and ASAH1, were validated.
- A novel glycoceramide (galabiosylceramide) was identified as an emphysema biomarker, supporting the ASAH1-emphysema genomic link.
Conclusions:
- Chronic obstructive pulmonary disease (COPD) exhibits distinct PBMC gene expression signatures in smokers.
- These molecular signatures, particularly those related to immune function and ceramide metabolism, offer potential diagnostic and therapeutic targets.
- PBMC gene expression profiles represent a promising avenue for understanding and managing COPD as a systemic disease.
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