Dataset Information

Ulcerative colitis: functional analysis of the in-depth proteome.

ABSTRACT: Background:Ulcerative colitis (UC) is one major form of inflammatory bowel disease. The cause and the pathophysiology of the disease are not fully understood and we therefor aim in this study to identify important pathophysiological features in UC from proteomics data. Methods:Colon mucosa biopsies from inflamed tissue of untreated UC patients at diagnosis and from healthy controls were obtained during colonoscopy. Quantitative protein data was acquired by bottom-up proteomics and furthermore processed with MaxQuant. The quantitative proteome data was analyzed with Perseus and enrichment data was analyzed by ClueGO for Cytoscape. Results:The generated proteome dataset is to-date the deepest from colon mucosa biopsies with 8562 identified proteins whereof 6818 were quantified in >?70% of the samples. We report abundance differences between UC and healthy controls and the respective p values for all quantified proteins in the supporting information. From this data set enrichment analysis revealed decreased protein abundances in UC for metallothioneins, PPAR-inducible proteins, fibrillar collagens and proteins involved in bile acid transport as well as metabolic functions of nutrients, energy, steroids, xenobiotics and carbonate. On the other hand increased abundances were enriched in immune response and protein processing in the endoplasmic reticulum, e.g. unfolded protein response and signal peptidase complex proteins. Conclusions:This explorative study describes the most affected functions in UC tissue. Our results complemented previous findings substantially. Decreased abundances of signal peptidase complex proteins in UC are a new discovery.

SUBMITTER: Schniers A

PROVIDER: S-EPMC6350310 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Ulcerative colitis: functional analysis of the in-depth proteome.

Schniers Armin A Goll Rasmus R Pasing Yvonne Y Sørbye Sveinung Wergeland SW Florholmen Jon J Hansen Terkel T

Clinical proteomics 20190129

<h4>Background</h4>Ulcerative colitis (UC) is one major form of inflammatory bowel disease. The cause and the pathophysiology of the disease are not fully understood and we therefor aim in this study to identify important pathophysiological features in UC from proteomics data.<h4>Methods</h4>Colon mucosa biopsies from inflamed tissue of untreated UC patients at diagnosis and from healthy controls were obtained during colonoscopy. Quantitative protein data was acquired by bottom-up proteomics and ...[more]

PMID: 30718987

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Project description:BackgroundPatients with ulcerative colitis (UC) are predisposed to colitis-associated colorectal cancer (CAC). However, the transcriptional mechanism of the transformation from UC to CAC is not fully understood.MethodologyFirstly, we showed that CAC and non-UC-associated CRC were very similar in gene expression. Secondly, based on multiple datasets for UC and CRC, we extracted differentially expressed (DE) genes in UC and CRC versus normal controls, respectively. Thirdly, we compared the dysregulation directions (upregulation or downregulation) between DE genes of UC and CRC in CRC-related functions overrepresented with the DE genes of CRC, and proposed a regulatory model to explain the CRC-like dysregulation of genes in UC. A case study for "positive regulation of immune system process" was done to reveal the functional implication of DE genes with reversal dysregulations in these two diseases.Principal findingsIn all the 44 detected CRC-related functions except for "viral transcription", the dysregulation directions of DE genes in UC were significantly similar with their counterparts in CRC, and such CRC-like dysregulation in UC could be regulated by transcription factors affected by pro-inflammatory stimuli for colitis. A small portion of genes in each CRC-related function were dysregulated in opposite directions in the two diseases. The case study showed that genes related to humoral immunity specifically expressed in B cells tended to be upregulated in UC but downregulated in CRC.ConclusionsThe CRC-like dysregulation of genes in CRC-related functions in UC patients provides hints for understanding the transcriptional basis for UC to CRC transition. A small portion of genes with distinct dysregulation directions in each of the CRC-related functions in the two diseases implicate that their reversal dysregulations might be critical for UC to CRC transition. The cases study indicates that the humoral immune response might be inhibited during the transformation from UC to CRC.

Dataset Information

Ulcerative colitis: functional analysis of the in-depth proteome.

Publications

Ulcerative colitis: functional analysis of the in-depth proteome.

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