Profiling Of Gene Expression In Idiopathic Pulmonary Fibrosis

p { margin-bottom: 0.08in; } Idiopathic pulmonary fibrosis (IPF) is a common, complex inflammatory lung disease with unknown etiology affecting RATIONALE: approximately 200,000 Americans. The rate of IPF progression differs among patients and the identification of IPF patients destined to progress and to require transplantation is an unmet medical need. We profiled gene expression patterns in peripheral blood mononuclear cells (PBMCs) from 41 IPF patients and 32 healthy METHODS: controls of European ancestry using Affymetrix Human Exon 1.0 ST Array. Spearman's rank correlation test was used to detect the relationship between gene expression level and IPF progression status or diffusing capacity of the lung for carbon monoxide (DLCO). Samples were grouped into four categories according to progression status: healthy, stable, mild progressive, and severe RESULTS: progressive. The expression of 1,388 genes were significantly correlated with IPF severity (adjusted P<0.01). Gene ontology analysis revealed ubiquitin-mediated proteolysis, T-cell receptor signaling pathway, PDGF signaling pathway, Notch signaling pathway, and MAPK signaling pathway as the most significantly dysregulated gene ontologies (P<0.01). Evaluation of the relationship between gene expression level and DLCO percent predicted, a reflection of disease severity revealed significant correlation (adjusted P<0.01) in 1,580 genes with the T cell receptor signaling pathway significantly overrepresented in addition to ECM-receptor interaction, calcium signaling pathway, focal adhesion, and hedgehog signaling pathway. Our results suggest that a substantial number of genes are likely involved in IPF pathobiology with disease progression CONCLUSIONS: providing identifiable heterogeneity in gene expression. Our findings may help elucidate the etiology of IPF and provide the potential for identifying novel biomarkers for diagnosis of IPF, and personalize the clinical approach to this complicated disease.