Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

40 IPF patients and 8 healthy controls

ABSTRACT: There is microscopic spatial and temporal heterogeneity of pathologic changes in idiopathic pulmonary fibrosis (IPF) lung tissue, which may relate to heterogeneity in pathophysiological mediators of disease and clinical progression. We measured gene expression in samples from lung biopsies or explants in order to assess relationships with pathological features and systemic biomarkers. RNA was extracted directly from lung tissue samples from 40 IPF patients or 8 healthy controls.

ORGANISM(S): Homo sapiens

SUBMITTER: Alex Abbas

PROVIDER: E-GEOD-53845 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis.

DePianto Daryle J DJ Chandriani Sanjay S Abbas Alexander R AR Jia Guiquan G N'Diaye Elsa N EN Caplazi Patrick P Kauder Steven E SE Biswas Sabyasachi S Karnik Satyajit K SK Ha Connie C Modrusan Zora Z Matthay Michael A MA Kukreja Jasleen J Collard Harold R HR Egen Jackson G JG Wolters Paul J PJ Arron Joseph R JR

Thorax 20140912 1

<h4>Background</h4>There is microscopic spatial and temporal heterogeneity of pathological changes in idiopathic pulmonary fibrosis (IPF) lung tissue, which may relate to heterogeneity in pathophysiological mediators of disease and clinical progression. We assessed relationships between gene expression patterns, pathological features, and systemic biomarkers to identify biomarkers that reflect the aggregate disease burden in patients with IPF.<h4>Methods</h4>Gene expression microarrays (N=40 IPF ...[more]

PMID: 25217476

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Project description:Intratracheal application of bleomycin is known to induce inflammatory and fibrotic reactions in the lung within a short period of time and histological features include infiltration of inflammatory cells, collagen deposition and obliteration of alveolar spaces. Because some of these features are found in patients with idiopathic pulmonary fibrosis (IPF), the bleomycin-induced lung fibrosis animal model is commonly used. However, exploratory treatments that were successfully used in this animal model and progressed to clinical trials lacked significant efficacy in humans. Here, the bleomycin-induced rat lung fibrosis model was studied using whole genome expression data that was collected at various time points and the relevance to human disease was evaluated through comparison with whole genome expression data from IPF patient-derived lung biopsies. The highest gene expression correlation between both species was observed in animals 7 days after bleomycin instillation. These gene expression signatures helped to identify a set of twelve novel disease-relevant translational gene markers that were able to separate IPF patients from controls. Furthermore, three Wnt/-catenin pathway-related genes that belong to this translational gene marker set showed, together with clinical diffusing capacity of the lung for carbon monoxide (DLCO) measurements, the potential to stratify IPF patients according to disease severity. Pirfenidone attenuated a subset of the translational gene markers in the bleomycin-induced fibrosis model, in particular those related to Wnt/-catenin-signaling. This novel translational gene marker panel offers improved possibilities to evaluate disease-modifying efficacy of novel therapeutic concepts in the bleomycin-induced rat lung fibrosis model and could be applied as a diagnostic and prognostic tool for IPF patient care. Comparison of bleomycin-treated and control rats after 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks and 8 weeks; 5 animals per group

Dataset Information

40 IPF patients and 8 healthy controls

Publications

Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis.

Similar Datasets

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