Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiles based on Pulmonary Artery Pressures in Pulmonary Fibrosis

ABSTRACT: Pulmonary Hypertension (PH) is a frequent complication of Pulmonary Fibrosis (PF). PH can be seen in PF in the abscence of hypoxemia, irrespective of the degree of fibrosis. At the same time, a consistent number of patients with advanced PF never develop PH. The pathogenesis of PH secondary to PF remains unclear. PF patients are often referred to lung transplantation, but they present a higher incidence of pimary graft dysfunction than other diseases. The cause of this is unknown, and the relationship with PH remains unclear. We used microarray to identifiy the gene expression profiles in PF patients with and without PH Fresh frozen lung samples were obtained from the recipients organs of 116 PF patients undergoing lung transplantation. RNA was extracted and hybridized on Affymetrix microarrays. Pulmonary artery pressures were recorded intraoperatively with right heart catheters before starting lung transplantation. Patients were divided in different groups based on the mean pulmonary artery pressure. We compared the gene expression profiles in the group with severe PH (mPAP>40 mmHg, n=17) and in that without PH (mPAP<20 mmHg, n=22)) and obtained a gene signature, which was used for clusterying analysis. The clustering analysis based on the gene signature was then validated in an Intermediate PH group (mPAP 21-39 mmHg, n=45) and in a Validation Set (n=32).

ORGANISM(S): Homo sapiens

SUBMITTER: Marco Mura

PROVIDER: E-GEOD-24988 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profiling in the lungs of patients with pulmonary hypertension associated with pulmonary fibrosis.

Mura Marco M Anraku Masaki M Yun Zhihong Z McRae Karen K Liu Mingyao M Waddell Thomas K TK Singer Lianne G LG Granton John T JT Keshavjee Shaf S de Perrot Marc M

Chest 20110811 3

<h4>Background</h4>Pulmonary hypertension (PH) associated with pulmonary fibrosis (PF) is a severe condition with poor outcome. It is unknown whether patients with PF with associated PH (APH) represent a distinct phenotype of the disease. We hypothesized that the lung tissue gene expression pattern of patients with APH has a characteristic profile when compared with patients with PF without APH. We sought to determine if different gene expression signatures in PF could be determined based on pul ...[more]

PMID: 21835902

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Project description:Objective: Pulmonary complications in systemic sclerosis (SSc), including pulmonary fibrosis (PF) and pulmonary arterial hypertension (PAH), are the leading cause of mortality. We compared the molecular fingerprint of SSc lung tissues and matching primary lung fibroblasts to those of normal donors, and patients with idiopathic pulmonary fibrosis (IPF) and idiopathic pulmonary arterial hypertension (IPAH). Methods: Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively. Results: We identified a consensus of 242 and 335 genes that were differentially expressed in lungs and primary fibroblasts, respectively. Enriched function groups in SSc-PF and IPF lungs included fibrosis, insulin-like growth factor signaling and caveolin-mediated endocytosis. Functional groups shared by SSc-PAH and IPAH lungs included antigen presentation, chemokine activity, and IL-17 signaling. Conclusion: Using microarray analysis on carefully phenotyped SSc and comparator lung tissues, we demonstrated distinct molecular profiles in tissues and fibroblasts of patients with SSc-associated lung disease compared to idiopathic forms of lung disease. Unique molecular signatures were generated that are disease- (SSc) and phenotype- (PF vs PAH) specific. These signatures provide new insights into pathogenesis and potential therapeutic targets for SSc lung disease. Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively.

Dataset Information

Gene expression profiles based on Pulmonary Artery Pressures in Pulmonary Fibrosis

Publications

Gene expression profiling in the lungs of patients with pulmonary hypertension associated with pulmonary fibrosis.

Similar Datasets

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