Dataset Information

Associations between cellular energy and pediatric inflammatory bowel disease patient response to treatment

ABSTRACT: Crohn’s disease (CD) and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of which the etiology and pathogenesis are not completely understood. In paediatric patients, the disease tends to be more severe and aggressive then in adults. Here, we perform a proteomic approach on ascending colon biopsies from 119 pediatric patients to characterize disease pathogenesis and the impacts of treatment. Consistent with previous findings, we report an altered proteome in IBD patients that indicates impaired mitochondrial function. Gene ontology revealed that proteins downregulated in inflammation are associated with metabolism, whereas upregulated proteins contribute to protein processing. A comparison of proteomes from CD patients before and after therapeutic intervention identified over 100 proteins that are significantly different between patients that responded and those that did not respond to therapy; creatine kinase B was elevated before treatment in patients with mucosal healing after treatment, whereas basigin increased after treatment in responsive patients.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Colon

DISEASE(S): Inflammatory Bowel Disease 1

SUBMITTER: Zhibin Ning

LAB HEAD: Daniel Figeys

PROVIDER: PXD024229 | Pride | 2021-08-26

REPOSITORIES: Pride

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Publications

Associations between Cellular Energy and Pediatric Inflammatory Bowel Disease Patient Response to Treatment.

Starr Amanda E AE Deeke Shelley A SA Ning Zhibin Z de Nanassy Joseph J Singleton Ruth R Benchimol Eric I EI Mack David R DR Stintzi Alain A Figeys Daniel D

Journal of proteome research 20210823 9

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are chronic diseases of the gastrointestinal tract, with an unknown etiology, that affect over 6.8 million people worldwide. To characterize disease pathogenesis, proteomic and bioinformatic analyses were performed on colon biopsies collected during diagnostic endoscopy from 119 treatment-naïve pediatric patients, including from 78 IBD patients and 41 non-IBD patients who served as controls. Due to the pre ...[more]

PMID: 34424714

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Project description:Inflammatory bowel disease (IBD) is a complex multi-factorial inflammatory disease with Crohn’s disease (CD) and ulcerative colitis (UC) being the two most common forms. A number of transcriptional profiling studies have provided compelling evidence that describe the role of protein-coding genes and microRNAs in modulating the immune responses in IBD. In the present study, we performed a genome-wide transcriptome profiling of lncRNAs and protein-coding genes in inflamed and non-inflamed colon pinch biopsies from the IBD patients using expression microarrays platform. In this study, we identified widespread dysregulation of lncRNAs and protein-coding genes in both inflamed and non-inflamed CD and UC compared to the healthy controls. In case of inflamed CD and UC (iCD and iUC), we identified 438 and 745 differentially expressed lncRNAs, respectively, while in case of the non-inflamed CD and UC (niCD and niUC), we identified 12 and 19 differentially expressed lncRNAs, respectively. We also observed significant enrichment (p-value < 0.001, Pearson’s Chi-squared test) for 96 differentially expressed lncRNAs and 154 protein-coding genes within the IBD susceptibility loci. Furthermore, we found strong positive expression correlations for the intersecting and cis-neighboring differentially expressed IBD loci-associated lncRNA-protein-coding gene pairs. The functional annotation analysis of differentially expressed genes revealed that they are involved in immune response, pro-inflammatory cytokine activity and MHC protein complex. The lncRNA expression profiling in both inflamed and non-inflamed CD and UC, successfully stratified IBD patients from the healthy controls. Taken together, the identified lncRNA transcriptional signature along with clinically relevant parameters suggests their potential as biomarkers in IBD. A total of 96 biopsy samples (including 6 samples used as technical replicates) extracted from different colonic locations from 45 patients (CD=13, UC=20, Controls=12) were profiled using Agilent Custom 8x60K format lncRNA expression microarray. In Gencode v15 lncRNA microarray design, each lncRNA transcript is targeted by two probes covering 22,001 lncRNA transcripts corresponding to 12,963 lncRNA genes. In addition, each array contains 17,535 randomly-selected protein-coding targets, of which 15,182 (unique 12,787) correspond to protein-coding genes.

Dataset Information

Associations between cellular energy and pediatric inflammatory bowel disease patient response to treatment

Publications

Associations between Cellular Energy and Pediatric Inflammatory Bowel Disease Patient Response to Treatment.

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