Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Systemic pro-fibrotic and pro-inflammatory response in patients with advanced cirrhosis

ABSTRACT: Objective: To evaluate gene expression profiles in patients with advanced cirrhosis compared with healthy controls (HC). Results: Patients with advanced cirrhosis exhibit an unbalanced systemic response involving pro-fibrotic / protective signatures that could be contributing to the pathogenesis of cirrhosis and also to that of the extra-hepatic complications of this disease.

ORGANISM(S): Homo sapiens

SUBMITTER: Raquel Almansa

PROVIDER: E-MTAB-3338 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Abstract BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has demonstrated to be a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature availble on gene expression markers associated to Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated to critical respiratory illness in this disease is not known to the present moment. RESULTS: By using Agilent microarray chips, we have profiled gene expression signatures in whole blood of 28 COPD patients hospitalized with distinct degree of respiratory compromise.12 of them needed of admission to the ICU, while 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparison of transcript levels between ICU and non ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to select, annotate and visualize genes by function and pathway (gene ontology). T-test evidenced 1501 genes differentially expressed between ICU and non ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients showed increased levels of neutrohil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This ?neutrophil signature? was paralleled by necessity of advanced respiratory and vital support, and presence of bacterial infection. CONCLUSION: study of transcriptomic signatures in blood suggests a central role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement / modulation of the expression of these genes could represent an option for clinical monitoring and treatment of severe COPD exacerbations. Keywords: COPD, critical, expression, gene, microarray, neutrophil, proteases.

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Systemic pro-fibrotic and pro-inflammatory response in patients with advanced cirrhosis

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