Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA218882 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is considered the surgery of choice for definitive management of familial adenomatous polyposis (FAP) and selected patients with ulcerative colitis (UC). However, this surgical treatment often associates with a long-term complication, pouchitis, which occurs mostly in UC patients. To better define the molecular background of pouchitis, the microarray-based survey was performed using pouch mucosal samples collected from 28 and 8 patients operated for UC and FAP, respectively. A number of 4771 genes was significantly differentiating uninflamed from inflamed mucosal samples, and their functional features were represented mostly by alerted metabolic and cell proliferation pathways. In contrast, functional analyses of aberrantly expressed probe sets between UC and FAP samples, irrespectively of mucosal inflammation status, revealed multiple pathways and terms which were linked to changes in immune response. Noteworthy, the comparison of uninflamed UC and FAP samples distinguished a set of 26 altered mRNAs including inflammation-related transcript encoding a Charcot-Leyden crystal (CLC) protein. The most discrete changes in gene expression profiles differentiating uninflamed UC and FAP mucosal samples were attributed to a Gene Ontology category innate immune response. Our study confirmed alterations of the immune responses as dominant in UC pouchitis which were earlier found in the studies using analyses of singular molecular elements. This observation may be important when managing IPAA patients. Each sample represents three biopsies taken from single patient, from the same areas of the lower part of the pouch mucosa (above the rectal cuff) during endoscopic examination. 28 patients underwent surgery for UC and 8 patients for FAP.
2014-05-01 | E-GEOD-50788 | biostudies-arrayexpress
Project description:A total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is considered the surgery of choice for definitive management of familial adenomatous polyposis (FAP) and selected patients with ulcerative colitis (UC). However, this surgical treatment often associates with a long-term complication, pouchitis, which occurs mostly in UC patients. To better define the molecular background of pouchitis, the microarray-based survey was performed using pouch mucosal samples collected from 28 and 8 patients operated for UC and FAP, respectively. A number of 4771 genes was significantly differentiating uninflamed from inflamed mucosal samples, and their functional features were represented mostly by alerted metabolic and cell proliferation pathways. In contrast, functional analyses of aberrantly expressed probe sets between UC and FAP samples, irrespectively of mucosal inflammation status, revealed multiple pathways and terms which were linked to changes in immune response. Noteworthy, the comparison of uninflamed UC and FAP samples distinguished a set of 26 altered mRNAs including inflammation-related transcript encoding a Charcot-Leyden crystal (CLC) protein. The most discrete changes in gene expression profiles differentiating uninflamed UC and FAP mucosal samples were attributed to a Gene Ontology category innate immune response. Our study confirmed alterations of the immune responses as dominant in UC pouchitis which were earlier found in the studies using analyses of singular molecular elements. This observation may be important when managing IPAA patients.
2014-05-01 | GSE50788 | GEO
Project description:UC pouchitis is a potential model of UC. We prospectively examined the pouch transcriptomes of UC and familial adenomatous polyposis (FAP) IPAA patients to unveil molecular mechanisms of UC pouchitis susceptibility. Methods: Total RNA was isolated using the AllPrep DNA/RNA Mini Kit (QIAGEN, Cat No. 8020). RNA quality was evaluated using Bioanalyzer (Agilent, Santa Clara, CA). All RNA samples displayed RNA Integrity Number (RIN) >7. RNAseq including cDNA library preparation was processed at the Genomics Core Facility of University of Chicago (https://fgf.uchicago.edu/). Total RNA in the amount of 100-500μg per sample was depleted of ribosomal RNA using the Ribo-Zero kit (Epicentre, Madison, WI). The directional (first strand) cDNA libraries were prepared following the guide of TruSeq Stranded Total RNA Sample Preparation kit. Results: Unlike FAP patients, UC subjects exhibited a large set of differentially expressed genes (DEGs) between pouch and pre-pouch mucosa as early as 4 months after pouch functionalization. Functional pathway analysis of DEGs in UC pouch revealed: (1) Gain of colon-associated gene expressions and loss of ileum associated gene expressions, (2) enhanced state of immune/inflammatory response, and (3) suppressed xenobiotic, lipid, and bile acid metabolic pathways. These changes were corroborated upon reanalysis of a published larger cross-sectional study of UC and FAP patients. Moreover, >70% of DEGs mapped to published IBD and normal colonic microarray datasets displayed directional changes consistent with active UC, but not Crohn's disease. Conclusions: UC patients exhibit a unique transcriptomic response to ileal pouch creation that can be observed well before disease. The transcriptome alterations provide insights into pouchitis
2016-05-11 | GSE81266 | GEO
Project description:<p>This study involved evaluation of the tissue associated microbiome of the ileal pouch following surgery for ulcerative colitis (UC) or familial adenomatous polyposis (FAP). Individuals were recruited, with biopsies taken from the ileal pouch and the pre-pouch ileum, microbial DNA was extracted and sequenced using 454 pyrosequencing. Total bacterial community structure and abundance were evaluated to determine which changes were characteristic of inflammatory phenotypes including pouchitis (inflammation of the ileal pouch) and a Crohn's disease-like phenotype.</p>
| phs000659 | dbGaP
Project description:<p>This study involved evaluation of the tissue associated microbiome of the ileal pouch following surgery for ulcerative colitis (UC) or familial adenomatous polyposis (FAP). Individuals were recruited, with biopsies taken from the ileal pouch and the pre-pouch ileum, microbial DNA was extracted and sequenced using 454 pyrosequencing. Total bacterial community structure and abundance were evaluated to determine which changes were characteristic of inflammatory phenotypes including pouchitis (inflammation of the ileal pouch) and a Crohn's disease-like phenotype.</p>
| phs000659.v1.p1 | EGA
Project description:The goal of the study was to compare the influence of Ileal pouch-anal anastomosis (IPAA) surgical treatment on patients with ulcerative colitis (UC) vs those with familial adenomatous polyposis (FAP). Stool samples were obtained at the time of clinic visit, immediately frozen and stored at -80oC until the assay. There were no exclusion criteria.
2014-09-10 | ST000277 | MetabolomicsWorkbench
Project description:Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the standard treatment for patients with severe treatment resistant ulcerative colitis (UC). Despite significant improvements in patient outcomes, up to 50% of patients will develop inflammation of the pouch (pouchitis) within 1-2 years following surgery. The pathogenesis of pouchitis is not well understood. Functionalization of UC pouches is associated with histological changes, whether these reflect changes in cellular identity and metaplasia remains unclear. To address this question, we generated cellular atlases of single-cell transcriptomes and accessible chromatin to assess the cellular composition, transcriptomic and epigenetic profiles in UC pouches.
2023-11-15 | GSE242086 | GEO
Project description:Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the standard treatment for patients with severe treatment resistant ulcerative colitis (UC). Despite significant improvements in patient outcomes, up to 50% of patients will develop inflammation of the pouch (pouchitis) within 1-2 years following surgery. The pathogenesis of pouchitis is not well understood. Functionalization of UC pouches is associated with histological changes, whether these reflect changes in cellular identity and metaplasia remains unclear. To address this question, we generated cellular atlases of single-cell transcriptomes and accessible chromatin to assess the cellular composition, transcriptomic and epigenetic profiles in UC pouches.
2023-11-15 | GSE242085 | GEO
Project description:Purpose: We evaluated clinical outcomes of patients with FGFR3-altered metastatic UC treated with ICB and investigate the underlying immunogenomic mechanisms of response and resistance Methods: 103 patients with metastatic UC treated with ICB at a single academic medical center from 2014-2018 were identified. Clinical annotation for demographics and cancer outcomes, as well as somatic DNA and RNA sequencing were performed. Objective response rate to ICB, progression-free survival, and overall survival was compared between patients with FGFR3 alterations and those without. RNA expression, including molecular subtyping and T cell receptor clonality, was also compared between FGFR3-altered and non-altered patients Results: Our findings from this dataset confirm that FGFR3-altered (n=17) and wild type (n=86) bladder cancers are equally responsive to ICB (12 vs 19%, p=0.73). Moreover, we demonstrate that despite being less inflamed, FGFR3-altered tumors have equivalent T cell receptor (TCR) diversity and that the balance of a CD8 T cell gene expression signature to immune suppressive features is an important determinant of ICB response Conclusions: Our work in a real world dataset validates prior observations from clinical trials but also extends this prior work to demonstrate that FGFR3-altered and wild type tumors have equivalent TCR diversity and that the balance of effector T cell to immune suppression signals are an important determinant of ICB response.
2021-06-08 | GSE176307 | GEO
Project description:Background & Aims: Genome-wide gene expression (GWGE) profiles of mucosal colonic biopsies have suggested the existence of a continuous inflammatory state in quiescent ulcerative colitis (UC). The aim of this study was to use DNA microarray-based GWGE profiling of mucosal colonic biopsies and isolated colonocytes from UC patients and controls in order to identify the cell types responsible for the continuous inflammatory state. Methods: Adjacent mucosal colonic biopsies were obtained endoscopically from the descending colon in patients with active UC (n=8), quiescent UC (n=9), and with irritable bowel syndrome (controls, n=10). After isolation of colonocytes and subsequent extraction of total RNA, GWGE data were acquired using Human Genome U133 Plus 2.0 GeneChip Array (Affymetrix, Santa Clara, CA). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P11 software (Umetrics, Umeå, Sweden). Results: A clear separation between active UC, quiescent UC and control biopsies were found, whereas the model for the colonocytes was unable to distinguish between quiescent UC and controls. The differentiation between quiescent UC and control biopsies was governed by unique profiles containing gene expressions with significant fold changes. These primarily belonged to the family of homeostatic chemokines revealing a plausible explanation to the abnormal regulated innate immune response seen in patients with UC. Conclusion: This study has demonstrated the presence of a continuous inflammatory state in quiescent UC, which seems to reflect an altered gene expression profile of lamina propria cells. Keywords: Colonocytes, continuous inflammation, mucosal colonic biopsies, gene expression profiles Adjacent mucosal colonic biopsies were attained endoscopically from the descending colon in patients with active UC (n=8), quiescent UC (n=9), and in controls (n=10). After extraction of total RNA, genome-wide gene expression data were acquired using Human Genome U133 Plus 2.0 GeneChip Array (Affymetrix, Santa Clara, CA). Amplification was required to obtain sufficient amounts of labelled complementary RNA (cRNA) target for analysis with arrays. Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P11 software (Umetrics, Umeå, Sweden).
2009-09-16 | E-GEOD-13367 | biostudies-arrayexpress