Dataset Information

Human colon biopsies (healthy and Ulcerative Colitis) LC-MS/MS

ABSTRACT: The etiology of the inflammatory bowel diseases, including ulcerative colitis, remains incomplete, but recent findings points to the involvement of complex host-microbial interactions. We hypothesized that an analysis of the proteins on the host-microbial interacting surface, the intestinal mucosa, could reveal novel insights into the diseases. Mucosal colonic biopsies were extracted by standard colonscopy from sigmoideum from 10 ulcerative colitis patients from non-inflammed tissue and 10 controls. The biopsies were immediately following extraction snap-frozen for protein analysis and the protein content of the biopsies was characterized by high-throughput quantative gel-free proteomics.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Allan Stensballe

PROVIDER: MSV000080833 | MassIVE | Fri Mar 31 17:12:00 BST 2017

SECONDARY ACCESSION(S): PXD001608

REPOSITORIES: MassIVE

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Publications

Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of Intestinal Biopsies.

Bennike Tue Bjerg TB Carlsen Thomas Gelsing TG Ellingsen Torkell T Bonderup Ole Kristian OK Glerup Henning H Bøgsted Martin M Christiansen Gunna G Birkelund Svend S Stensballe Allan A Andersen Vibeke V

Inflammatory bowel diseases 20150901 9

<h4>Background</h4>The etiology of the inflammatory bowel diseases, including ulcerative colitis (UC), remains incompletely explained. We hypothesized that an analysis of the UC colon proteome could reveal novel insights into the disease etiology.<h4>Methods</h4>Mucosal colon biopsies were taken by endoscopy from noninflamed tissue of 10 patients with UC and 10 controls. The biopsies were either snap-frozen for protein analysis or prepared for histology. The protein content of the biopsies was c ...[more]

PMID: 25993694

Publication: 1/2

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Project description:Background and aims: Mucosal abnormalities are potentially important in the primary pathogenesis of ulcerative colitis (UC). We investigated the mucosal transcriptomic expression profiles of biopsies from patients with UC and healthy controls (HC), taken from macroscopically non-inflamed tissue from the terminal ileum and three colonic locations with the objective of identifying abnormal molecules that might be involved in disease development. Methods: Whole-genome transcriptional analysis was performed on intestinal biopsies taken from 24 UC, 26 HC and 14 patients with CrohnM-bM-^@M-^Ys disease. Differential gene expression analysis was performed at each tissue location separately and results were then meta-analysed using FisherM-bM-^@M-^Ys method. Significantly differentially expressed genes were validated using qPCR. Gene location within the colon was determined using immunohistochemistry, subcellular fractionation, electron and confocal microscopy. DNA methylation was quantified by pyrosequencing. Results: Seven probes were abnormally expressed throughout the colon in UC patients with Family with sequence similarity member 5 C (FAM5C) being the most significantly underexpressed. Attenuated expression of FAM5C in UC was independent of inflammation, unrelated to phenotype or treatment, and remained low at rebiopsy approximately 23 months later. FAM5C is localised to the brush border of the colonic epithelium and expression is influenced by DNA methylation within its promoter. Conclusion: Genome-wide expression analysis of non-inflamed mucosal biopsies from UC patients identified FAM5C as significantly under-expressed throughout the colon in a major sub-set of patients with UC. Low levels of this gene could predispose to or contribute to the maintenance of the characteristic mucosal inflammation seen in this condition. Total RNA was extracted from the intestinal biopsies taken from macroscopically normal mucosa in the rectum, descending colon, ascending colon and terminal ileum in clinically quiescent Ulcerative colitis and Crohn's disease patients and compared to healthy controls. Normalized data for 26,261 probes out of 47,323 only. Criteria for inclusion not specified. The non-normalized matrix contains the complete non-normalized data for all probes.

Project description:Introduction: Many gene expression studies of colitis-associated colorectal cancer (CA-CRC) in patients with ulcerative colitis (UC) have focused on identification of molecular drivers of progression of UC to CA- CRC. However, they have primarily studied cancerous mucosal biopsies, an approach which primarily may identify the characteristics of the established cancer mucosa and not the early molecular events driving the progression. Long-standing mucosal inflammation is suspected to be one of the main drivers of CA-CRC. Still, not all patients with UC progress and develop cancer. We hypothesise that patients with UC, who have progressed to neoplasia (progressors), have a different molecular profile of inflammation than non-progressors. Methods: We performed transcriptome profiling on 143 mucosal biopsies from non-neoplastic colonic segments of 14 UC progressors and 30 UC non-progressors. In addition, we performed profiling of lymphocyte infiltration to the mucosa of biopsies taken adjacent to biopsies used for transcriptomic analysis. Results: We found a characteristic gene expression profile for inflamed mucosa of UC progressors, which primarily is associated with progression of UC to dysplasia or cancer as opposed to long duration of disease. The gene expression profile suggests that the inflamed tissue of UC progressors is negatively enriched for biological processes such as adaptive immune responses and complement system activity and positively enriched for biological processes related to detoxification. Moreover, we found that the microenvironment in the inflamed mucosa of progressors differs from non-progressors by having fewer infiltrating B cells and less lymphoid aggregates. Conclusions: We found that inflammation of UC patients, who have progressed to dysplasia or cancer, has a different gene expression profile than that of UC non-progressors. Importantly, this profile was primarily associated with progression of disease as opposed to duration of disease. The inflamed mucosa of UC progressors may have lower levels of lymphoid organ-initiating and immune cell- attracting signals and fewer immune cells infiltrating the mucosa. Consequently, progressors may lack the ability to mount sufficient adaptive immune responses necessary to counteract driving forces of malignant transformation in UC.