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Genome-wide maps of circulating miRNA biomarkers for Ulcerative Colitis

ABSTRACT: Circulating miRNAs has recently emerged as clinically relevant blood-based biomarkers for disease detection, tracking and prediction. The stability of these species combined with easy accessibility in circulation makes them attractive candidates for rapid and economic surveillance of broad spectrum disorders requiring invasive diagnosis.In this work we directly assess the utility of non-invasive blood-based biomarkers as an alternative strategy to accurately predict incidences of Ulcertaive Colitis. Whole genome miRNA expression levels in Microvescicles , Peripheral Blood Mononuclear Cells (PMBC) and platelets from a cohort of 20 Ulcerative Colitis patients and 20 normal individuals were measured using Affymetric microarrays.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE32273 | GEO | 2012/02/21

SECONDARY ACCESSION(S): PRJNA147323

REPOSITORIES: GEO

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Project description:Objective: Ulcerative colitis (UC) is a chronic disease with rising incidence and unclear etiology. The application of mass spectrometry-based post-genomic analysis methods shall support the development of molecular biomarker signatures providing status information with regard to UC pathomechanisms. Design: Pathomechanisms characteristic for UC were assessed by proteome profiling of human tissue specimen, obtained from five distinct colon locations each of 12 patients. Systemic disease-associated alterations were investigated by mass spectrometry-based multi-omics analyses comprising proteins, metabolites and eicosanoids of plasma obtained from UC patients during disease and upon remission in comparison to healthy controls. Results: Proteome profiling results identified colitis-associated activation of neutrophils, macrophages, B- and T-cells, platelets, fibroblasts and endothelial cells and indicated hypoxic stress, as well as a general reduction of mitochondrial proteins accompanying the establishment of apparent healing-promoting activities as well as scar formation. While the immune cells mainly contributed pro-inflammatory proteins, the colitis-associated epithelial cells, fibroblasts, endothelial cells and platelets predominantly formed anti-inflammatory and healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulation of bile acids, eicosanoids and gut microbiome-derived metabolites. Upon remission, several, but not all, molecular candidate biomarker levels recovered to normal levels. These findings may indicate that pathomechanisms related to gut functions, gut microbiome status, microvascular damage and metabolic dysregulation associated with hypoxia may do not resolve uniformly upon remission. Conclusions: The establishment of disease-associated biomarker profiles related to molecular UC pathomechanisms may support the establishment of bioassays with improved prognostic power aiding individualized therapy.

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Genome-wide maps of circulating miRNA biomarkers for Ulcerative Colitis

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