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MRNA and small RNA associated with Crohn's disease behavior [RNA-Seq]

ABSTRACT: There is a need for reliable prognostic markers that can guide therapeutic intervention in Crohn’s disease (CD). We examined whether different behavioral phenotypes in CD can be classified based on colonic miRNA or mRNA expression and if miRNAs have prognostic utility for CD. We perform high-throughput sequencing of small RNA and mRNA isolated from colon tissue from CD patients and non-IBD (NIBD) controls. To identify miRNA and genes associated with specific behavioral phenotypes of CD, patients were stratified according to disease behavior (non-stricturing, non-penetrating; stricturing; penetrating) and compared miRNA profiles in each class with those of the NIBD group. Using a novel statistical simulation approach applied to colonic RNA-seq data for CD patients and NIBD controls, we identify at drivers of gene expression profiles associated with CD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66207 | GEO | 2015/07/15

SECONDARY ACCESSION(S): PRJNA276116

REPOSITORIES: GEO

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mRNA and small RNA associated with Crohn's disease behavior [ncRNA-Seq]

Project description:There is a need for reliable prognostic markers that can guide therapeutic intervention in Crohn’s disease (CD). We examined whether different behavioral phenotypes in CD can be classified based on colonic miRNA or mRNA expression and if miRNAs have prognostic utility for CD. We perform high-throughput sequencing of small RNA and mRNA isolated from colon tissue from CD patients and non-IBD (NIBD) controls. To identify miRNA and genes associated with specific behavioral phenotypes of CD, patients were stratified according to disease behavior (non-stricturing, non-penetrating; stricturing; penetrating) and compared miRNA profiles in each class with those of the NIBD group. Using a novel statistical simulation approach applied to colonic RNA-seq data for CD patients and NIBD controls, we identify at drivers of gene expression profiles associated with CD.

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Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn’s disease

Project description:Crohn's disease (CD) is a chronic inflammatory gut disorder. Molecular mechanisms underlying the clinical heterogeneity of CD remain poorly understood. MicroRNAs (miRNAs) are important regulators of gut physiology and several have been implicated in the pathogenesis of adult CD. However, there is a dearth of large-scale miRNA studies for pediatric CD. We hypothesized that specific miRNAs uniquely mark pediatric CD. We performed small RNA-sequencing of patient-matched non-inflamed colon and ileum biopsies from treatment-naïve pediatric patients with CD (n=169) and a control cohort (n=108). Comprehensive miRNA analysis revealed 58 miRNAs altered in pediatric CD. Notably, multinomial logistic regression analysis revealed that index levels of ileal miR-29 are strongly predictive of severe inflammation and stricturing. Transcriptomic analyses of transgenic mice overexpressing miR-29 show a significant reduction of the tight junction protein gene Pmp22 and classic Paneth cell markers. The dramatic loss of Paneth cells was confirmed by histologic assays. Moreover, we also found that pediatric CD patients with elevated miR-29 exhibit significantly lower Paneth cell counts, increased inflammation scores, and reduced levels of PMP22. These findings strongly indicate that miR-29 up-regulation is a distinguishing feature of pediatric CD, highly predictive of severe phenotypes, and associated with inflammation and Paneth cell loss.

2022-12-23 | GSE221261 | GEO

Colonic miR-31 is a molecular stratifier and prognostic determinant of Crohn’s disease [adult]

Project description:The clinical course of Crohn's disease (CD) is highly heterogeneous, confounding effective personalized therapy. There is a critical need to better understand the cellular mechanisms responsible for the variability in disease presentation and response to therapeutic modalities. We carried out whole transcriptome profiling in colon tissue from adult CD patients and controls and found that CD patients segregate into the same two molecular subtypes based on mRNA, long non-coding RNA, or microRNA profiles. MicroRNA-31 (miR-31) in colonic epithelium was identified as a primary contributor to this molecular stratification. We further performed small RNA-seq on formalin-fixed paraffin embedded colon and ileum biopsies obtained at the time of diagnosis from 130 treatment-naïve pediatric CD patients and controls. Colonic expression of miR-31 in pediatric patients was identified as predictive of either medically refractory rectal CD or fibrostenotic ileal CD. Our study reveals miRNAs as important molecular stratifiers and prognostic determinants of CD subtypes.

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Expression data from intestinal mucosa of patients with CD under anti-TNF-alpha therapy.

Project description:Crohn's Disease (CD) is a chronic inflammatory disease of the intestinal tract. We performed a whole-genome transcriptional analysis using colonic biopsies from CD patients before and after anti-TNF-α therapy. Involved colonic samples from Crohn's disease patients and healthy colonic samples from non-inflammatory controls were collected for RNA extraction and hybridization on Affymetrix microarrays. Inclusion criteria for CD patients were: age between 18 and 70, diagnosis of CD established at least 4 months before inclusion and exclusion of concomitant infection. Active disease was defined by endoscopic and clinical score: endoscopic active disease was defined as a CD endoscopic index of severity (CDEIS) of 5 or more and the presence of large ulcers (> 0.5 cm diameter) in at least one of the explored segments. Clinical activity was defined as a CD activity index (CDAI) above 150. Finally, a total of 39 biopsies were analyzed: 17 healthy controls, 10 active CD without anti-TNF therapy, 5 active CD with anti-TNF therapy (non-responders) and 7 inactive CD with anti-TNF therapy (responders).

2014-04-08 | E-GEOD-52746 | biostudies-arrayexpress

Myeloid-stromal subtypes reveal NOD2-mediated Crohn's and rescue pathways

Project description:Crohn’s disease (CD) is a chronic inflammatory intestinal disease, often characterized by aberrant healing and stricturing complications. Mechanisms underlying NOD2-pathogenicity and salvage pathways in anti-TNF and refractory patients remain largely uncharacterized. Here we show that loss of NOD2 function leads to aberrant activated fibroblast and macrophage homeostasis through the upregulation of a pathogenic signature, and propose new precision therapeutic approaches involving gp130 blockade for select CD patients, to potentially supplement anti-TNF therapy

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Project description:This dataset includes RNA-seq data from ileal and colonic biopsies at time of diagnosis for treatment-naive, uncomplicated Crohn's disease (CD) patients and matched controls. This is includes 56 CD patients each for ileal and colonic tissue and for controls, 46 colonic samples and 45 ileal samples. Clinical characteristics such as development of complications, disease remission, or progression to surgery were recorded with a mean follow-up of 6 years.

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2011-01-04 | E-GEOD-26305 | biostudies-arrayexpress

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Project description:Based on genetic risk factors and natural history, Crohn’s disease (CD) can be separated in two entities, an ileal and a colonic disease. Protein based-approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes. In this work, we compared the proteome of ulcer edge to the one of paired control tissue in ileum and colon of CD patients. We revealed that ileal and colonic ulcer edge can be distinguished by a differential distribution of epithelial–mesenchymal transition proteins, neutrophil degranulation proteins and ribosomal proteins. In ileal and colonic ulcer edge, we found a quasi-systematic increase of the proteins implicated in the pathway of protein processing in endoplasmic reticulum and a quasi-systematic decrease of mitochondrial proteins. Our study provides for the first time protein-based evidences showing partly distinct pathophysiological processes associated to ileal and colonic ulcer edge in CD. This could constitute a first step toward the development of gut segment-specific diagnostic markers and therapeutics.

2019-07-15 | PXD012284 | Pride

Expression data from intestinal mucosa of patients with CD under anti-TNF-alpha therapy.

2014-04-08 | GSE52746 | GEO

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