Aneuploidy-associated gene expression signatures characterize malignant transformation in ulcerative colitis.

Abstract:

BACKGROUND:Malignant transformation in ulcerative colitis (UC) is associated with pronounced chromosomal instability, reflected by aneuploidy. Although aneuploidy can precede primary cancer diagnosis in UC for more than a decade, little is known of its cellular consequences. METHODS:Whole-genome gene expression analysis was applied to noninflamed colon mucosa, mucosal biopsies of patients with UC, and UC-associated carcinomas (UCCs). DNA image cytometry was used to stratify samples into ploidy types. Differentially expressed genes (DEGs) were analyzed by Ingenuity Pathway Analysis and validated by real-time quantitative PCR. RESULTS:Gene expression changes were more pronounced between normal mucosa and UC (2587 DEGs) than between UC and UCC (827 DEGs). Cytometry identified colitis patients with euploid or aneuploid mucosa biopsies, whereas all UCCs were aneuploid. However, 1749 DEGs distinguished euploid UC and UCCs, whereas only 15 DEGs differentiated aneuploid UC and UCCs. A total of 16 genes were differentially expressed throughout the whole sequence from normal controls to UCCs. Particularly, genes pivotal for chromosome segregation (e.g., SMC3 and NUF2) were differentially regulated along aneuploidy development. CONCLUSIONS:The high number of DEGs between normal mucosa and colitis is dominated by inflammatory-associated genes. Subsequent acquisition of aneuploidy leads to subtle but distinct transcriptional alterations, revealing novel target genes that drive genomic instability and thus carcinogenesis. The gene expression signature of malignant phenotypes in aneuploid UC suggests that these lesions might need to be considered as severe as high-grade dysplasia.

journal_name

Inflamm Bowel Dis

authors

Gerling M,Nousiainen K,Hautaniemi S,Krüger S,Fritzsche B,Homann N,Bruch HP,Auer G,Roblick UJ,Ried T,Habermann JK

doi

10.1097/MIB.0b013e31827eeaa4

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

691-703

issue

4

eissn

1078-0998

issn

1536-4844

journal_volume

19

pub_type

杂志文章
  • Racial differences in disease phenotypes in patients with Crohn's disease.

    abstract:BACKGROUND:Our objectives were to assess the differences in perforating disease behavior, disease severity, and extraintestinal manifestations (EIM) in patients with Crohn's disease (CD) by race. MATERIALS AND METHODS:We identified outpatients with CD evaluated at the University of Maryland Gastroenterology Faculty Pr...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/01.MIB.0000217767.98389.20

    authors: Cross RK,Jung C,Wasan S,Joshi G,Sawyer R,Roghmann MC

    更新日期:2006-03-01 00:00:00

  • Antimicrobial peptide response to blood translocation of bacterial DNA in Crohn's disease is affected by NOD2/CARD15 genotype.

    abstract:BACKGROUND:Blood translocation of bacterial-DNA has been described in patients with Crohn's disease (CD). The host's immune cell types cooperate to respond against bacterial insults. Some antimicrobial peptides are inducible after culture with bacterial products and a linkage has been established between them and NOD2/...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21537

    authors: Gutiérrez A,Holler E,Zapater P,Sempere L,Jover R,Pérez-Mateo M,Schoelmerich J,Such J,Wiest R,Francés R

    更新日期:2011-08-01 00:00:00

  • Characterization of hepatic abnormalities in children with inflammatory bowel disease.

    abstract::: We sought to characterize the incidence, nature, and course of liver disease in children with inflammatory bowel disease (IBD). Chart review identified 555 subjects (318 Crohn's disease [CD], 237 ulcerative colitis [UC]). An alanine aminotransferase measurement of ≥80 U/L was used to identify the presence of a hepat...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:

    authors: Hyams J,Markowitz J,Treem W,Davis P,Grancher K,Daum F

    更新日期:1995-04-01 00:00:00

  • Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.

    abstract:BACKGROUND:A notable proportion of patients with inflammatory bowel disease (IBD) are switched from infliximab (IFX) to adalimumab (ADL). We investigated if immunogenicity of IFX influenced immunogenicity and clinical outcomes of later ADL therapy. METHODS:Single-center cohort study including all patients with IBD ass...

    journal_title:Inflammatory bowel diseases

    pub_type: 临床试验,杂志文章

    doi:10.1097/MIB.0000000000000138

    authors: Frederiksen MT,Ainsworth MA,Brynskov J,Thomsen OO,Bendtzen K,Steenholdt C

    更新日期:2014-10-01 00:00:00

  • Population-based case-control study of measles, mumps, and rubella and inflammatory bowel disease.

    abstract:BACKGROUND:Previous controversy was generated over the hypothesis that a paramyxovirus such as measles or vaccination against such viruses might be causally associated with inflammatory bowel disease (IBD). We aimed to determine if Crohn's disease (CD) or ulcerative colitis (UC) subjects are more likely to be seroposit...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.20089

    authors: Bernstein CN,Rawsthorne P,Blanchard JF

    更新日期:2007-06-01 00:00:00

  • Length and type of recurrent ileitis after ileal resection correlate with presurgical features in Crohn's disease.

    abstract:SUMMARY:: Crohn's disease of the terminal ileum usually recurs after an ileocolonic resection. To compare the length and the disease behavior of recurrent ileitis with the presurgical disease characteristics, we studied 31 consecutive patients who had recurrent Crohn's disease symptoms and who had undergone an ileoceca...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:

    authors: Dʼhaens G,Baert F,Gasparaitis A,Hanauer S

    更新日期:1997-01-01 00:00:00

  • Contraception, Venous Thromboembolism, and Inflammatory Bowel Disease: What Clinicians (and Patients) Should Know.

    abstract::The peak incidence of the inflammatory bowel diseases (IBDs) is between the second and fourth decades of life, which coincides with prime reproductive years. Unplanned or mistimed pregnancies may account for nearly half of all pregnancies and are associated with adverse consequences such as a higher risk of delayed pr...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izz025

    authors: Limdi JK,Farraye J,Cannon R,Woodhams E,Farraye FA

    更新日期:2019-09-18 00:00:00

  • Increased Prevalence of Inflammatory Bowel Disease in Patients with Mutations in Genes Encoding the Receptor Subunits for TGFβ.

    abstract:BACKGROUND:TGFβ is a multifunctional cytokine that is critical in regulating mucosal immunity. Murine studies have revealed that disruption of canonical TGFβ signaling leads to systemic inflammation including colitis. Loeys-Dietz syndrome (LDS) results from heterozygous mutations in the genes encoding the subunits of t...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000872

    authors: Guerrerio AL,Frischmeyer-Guerrerio PA,Huang C,Wu Y,Haritunians T,McGovern DPB,MacCarrick GL,Brant SR,Dietz HC

    更新日期:2016-09-01 00:00:00

  • Apical Periodontitis in Patients With Inflammatory Bowel Disease: A Puppet Master?

    abstract::Focal infection theory posits that periodontal pathobionts play a causal role in initiating or exacerbating diseases. Periodontal disease is a common inflammatory, multifactorial disease of the periodontal tissues. The main factor for inflammation is mature dental plaque with the presence of pathogens in the microbial...

    journal_title:Inflammatory bowel diseases

    pub_type: 评论,社论

    doi:10.1093/ibd/izz129

    authors: Barta Z

    更新日期:2020-01-06 00:00:00

  • Therapy with anti-TNFα antibody enhances number and function of Foxp3(+) regulatory T cells in inflammatory bowel diseases.

    abstract:BACKGROUND:Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFα, hyperactivation of proinflammatory effector T cells (Teffs) and inefficient control by regulatory CD4(+) CD25(+) Foxp3(+) T cells (Tregs). The aim of this prospective study was to investigate the short-term impact of treatment of I...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21308

    authors: Boschetti G,Nancey S,Sardi F,Roblin X,Flourié B,Kaiserlian D

    更新日期:2011-01-01 00:00:00

  • Prevalence and Risk Factors of Substance Use Disorder in Inflammatory Bowel Disease.

    abstract:BACKGROUND:Substance use disorders (SUDs) impose a substantial individual and societal burden; however, the prevalence and associated factors in persons with inflammatory bowel disease (IBD) are largely unknown. We evaluated the prevalence and risk factors of SUD in an IBD cohort. METHODS:Inflammatory bowel disease pa...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izaa014

    authors: Carney H,Marrie RA,Bolton JM,Patten SB,Graff LA,Bernstein CN,Kowalec K

    更新日期:2021-01-01 00:00:00

  • Providing disease-related information worsens health-related quality of life in inflammatory bowel disease.

    abstract:BACKGROUND:Patients with inflammatory bowel disease (IBD) have identified a need for more information about their disease. PURPOSE:To assess the effect of an educational intervention on health-related quality of life (HRQOL) in patients with IBD. METHODS:Consecutive ambulatory IBD patients were randomized to receive ...

    journal_title:Inflammatory bowel diseases

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00054725-200207000-00005

    authors: Borgaonkar MR,Townson G,Donnelly M,Irvine EJ

    更新日期:2002-07-01 00:00:00

  • Micronutrient deficiencies in inflammatory bowel disease: from A to zinc.

    abstract::Inflammatory bowel disease (IBD) has classically been associated with malnutrition and weight loss, although this has become less common with advances in treatment and greater proportions of patients attaining clinical remission. However, micronutrient deficiencies are still relatively common, particularly in CD patie...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1002/ibd.22906

    authors: Hwang C,Ross V,Mahadevan U

    更新日期:2012-10-01 00:00:00

  • Skin side effects of inflammatory bowel disease therapy.

    abstract::Skin manifestations are common in patients suffering from inflammatory bowel disease (IBD) and can be associated with the disease itself, with nutritional deficiencies, or with therapy. All drugs currently used for treating IBD have the potential to cause dermatologic manifestations that can have a wide range of clini...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1097/MIB.0b013e3182802c07

    authors: Torres J,Buche S,Delaporte E,Colombel JF

    更新日期:2013-04-01 00:00:00

  • Hospital Admissions, Biological Therapy, and Surgery in Familial and Sporadic Cases of Inflammatory Bowel Disease: A Population-Based Cohort Study 1977-2011.

    abstract:BACKGROUND:Easily accessible predictors of disease course in inflammatory bowel disease (IBD) are scarce, and it remains largely unknown whether a family history of IBD predicts the course of Crohn's disease (CD) and ulcerative colitis (UC). We aimed to compare the course of disease in familial and sporadic cases of IB...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000545

    authors: Trier Moller F,Andersen V,Andersson M,Jess T

    更新日期:2015-12-01 00:00:00

  • Factors Affecting Clinical and Endoscopic Outcomes of Placebo Arm in Trials of Biologics and Small Molecule Drugs in Ulcerative Colitis: A Meta-Analysis.

    abstract:BACKGROUND:Previous systematic cumulative analyses of the placebo arm in ulcerative colitis (UC) were limited by the wide heterogeneity in the scores and definitions of response. We aimed at estimating the placebo rates of remission, response, and mucosal healing (MH) in phase 2 and 3 randomized placebo-controlled tria...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,meta分析

    doi:10.1093/ibd/izy365

    authors: Macaluso FS,Maida M,Ventimiglia M,Renna S,Cottone M,Orlando A

    更新日期:2019-05-04 00:00:00

  • Colitis and colon cancer in WASP-deficient mice require helicobacter species.

    abstract:BACKGROUND:Wiskott-Aldrich syndrome protein-deficient patients and mice are immunodeficient and can develop inflammatory bowel disease. The intestinal microbiome is critical to the development of colitis in most animal models, in which Helicobacter spp. have been implicated in disease pathogenesis. We sought to determi...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0b013e318295fd8f

    authors: Nguyen DD,Muthupalani S,Goettel JA,Eston MA,Mobley M,Taylor NS,McCabe A,Marin R,Snapper SB,Fox JG

    更新日期:2013-09-01 00:00:00

  • Healing of intestinal inflammation by IL-22.

    abstract::An interleukin (IL)-10 family cytokine, IL-22 is characterized by several unique biological properties, including 1) the target restricted to innate cells; 2) the distinct expression pattern between large and small intestines; 3) alteration of the cellular source depending on several factors; 4) the dual abilities to ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1002/ibd.22929

    authors: Mizoguchi A

    更新日期:2012-09-01 00:00:00

  • Interrogating the Gut-Brain Axis in the Context of Inflammatory Bowel Disease: A Translational Approach.

    abstract::This review examines preclinical and clinical studies relevant to our understanding of how the bidirectional gut-brain axis influences the natural history of inflammatory bowel disease. Preclinical studies provide proof of concept that preexisting behavioral illness, such as depression, results in increased susceptibi...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izaa004

    authors: Collins SM

    更新日期:2020-03-04 00:00:00

  • Health-related quality of life in patients with ulcerative colitis after a 10-year disease course: results from the IBSEN study.

    abstract:BACKGROUND:Ulcerative colitis (UC) negatively affects health-related quality of life (HRQoL), but population-based and long-term data on this topic are scarce. Our aim was to determine the HRQoL in UC patients after a 10-year disease duration. METHODS:UC patients from a population-based inception cohort met at a presc...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21863

    authors: Hoivik ML,Moum B,Solberg IC,Cvancarova M,Hoie O,Vatn MH,Bernklev T,IBSEN Study Group.

    更新日期:2012-08-01 00:00:00

  • Patient-reported Anxiety: A Possible Predictor of Pediatric Inflammatory Bowel Disease Health Care Use.

    abstract:BACKGROUND:Anxiety is linked with adverse health-related outcomes and increased health-seeking behaviors among patients with chronic illness. Yet, this relationship has received little attention in pediatric inflammatory bowel disease. The aim of this study was to examine whether anxiety symptoms predicted youth at inc...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000864

    authors: Reigada LC,Satpute A,Hoogendoorn CJ,Cohen BH,Lai J,Bao R,Dubinsky MC,Benkov KJ

    更新日期:2016-09-01 00:00:00

  • Risk Factors and Clinical Outcomes Associated with Cytomegalovirus Colitis in Patients with Acute Severe Ulcerative Colitis.

    abstract:BACKGROUND:Cytomegalovirus (CMV) colitis can contribute to an unfavorable outcome of acute severe ulcerative colitis (ASUC). The purpose of this study was to evaluate the clinical outcomes of ASUC according to the CMV status and identify risk factors for CMV colitis in patients with ASUC. METHODS:We retrospectively an...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000675

    authors: Lee HS,Park SH,Kim SH,Kim J,Choi J,Lee HJ,Kim WS,Lee JM,Kwak MS,Hwang SW,Yang DH,Kim KJ,Ye BD,Byeon JS,Myung SJ,Yoon YS,Yu CS,Kim JH,Yang SK

    更新日期:2016-04-01 00:00:00

  • Approach to corticosteroid-dependent and corticosteroid-refractory Crohn's disease.

    abstract::Corticosteroids are considered a drug of choice for the treatment of patients with moderately to severely active Crohn's disease (CD), an inflammatory bowel disease characterized by chronic recurrent flares of disease activity. However, among patients receiving corticosteroid therapy for induction of remission, 20% ha...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1002/ibd.3780070506

    authors: Lichtenstein GR

    更新日期:2001-05-01 00:00:00

  • A new oral delivery system for 5-ASA: preliminary clinical findings for MMx.

    abstract:BACKGROUND:Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how ...

    journal_title:Inflammatory bowel diseases

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1097/01.mib.0000158386.25660.1e

    authors: Prantera C,Viscido A,Biancone L,Francavilla A,Giglio L,Campieri M

    更新日期:2005-05-01 00:00:00

  • Galectin-2 and -4, but not galectin-1, promote intestinal epithelial wound healing in vitro through a TGF-beta-independent mechanism.

    abstract:BACKGROUND:Inflammatory bowel diseases (IBDs) are characterized by various degrees of mucosal surface damage and subsequent impairment of the intestinal barrier function. Resealing of the epithelial barrier requires intestinal cell migration and proliferation. Galectins are increasingly recognized as novel regulators o...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.20499

    authors: Paclik D,Lohse K,Wiedenmann B,Dignass AU,Sturm A

    更新日期:2008-10-01 00:00:00

  • Differentiation Between Pediatric Irritable Bowel Syndrome and Inflammatory Bowel Disease Based on Fecal Scent: Proof of Principle Study.

    abstract:Background:The diagnostic work-up of pediatric irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) commonly includes invasive tests for discrimination from inflammatory bowel disease (IBD). As this carries a high burden on patients, an ongoing need exists for development of no...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izy151

    authors: Bosch S,van Gaal N,Zuurbier RP,Covington JA,Wicaksono AN,Biezeveld MH,Benninga MA,Mulder CJ,de Boer NKH,de Meij TGJ

    更新日期:2018-10-12 00:00:00

  • Differential role of tumor necrosis factor receptors in TNBS colitis.

    abstract:BACKGROUND:Tumor necrosis factor alpha (TNFalpha) plays a central role in the pathology of T helper 1-mediated colitis such as Crohn's disease; however, the role of its 2 receptors in mediating pathology has not been fully explored. METHODS:Trinitrobenzene sulfonic acid colitis was used to induce colitis in mice lacki...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/01.mib.0000163698.34592.30

    authors: Ebach DR,Newberry R,Stenson WF

    更新日期:2005-06-01 00:00:00

  • Reciprocal regulation of the survival and apoptosis of Th17 and Th1 cells in the colon.

    abstract:BACKGROUND:The immediate early response gene X-1 (IEX-1) is a stress-inducible gene involved in the regulation of cell growth, apoptosis and inflammation. METHODS:Acute colitis was induced by treatment of IEX-1 knockout (KO) and wild type (WT) control mice with dextran sulfate sodium (DSS), whereas chronic colitis was...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21772

    authors: Ustyugova IV,Zhi L,Wu MX

    更新日期:2012-02-01 00:00:00

  • Acute Colitis Drives Tolerance by Persistently Altering the Epithelial Barrier and Innate and Adaptive Immunity.

    abstract:BACKGROUND:Inflammatory bowel disease (IBD) has a remitting and relapsing disease course; however, relatively little is understood regarding how inflammatory damage in acute colitis influences the microbiota, epithelial barrier, and immune function in subsequent colitis. METHODS:Mice were administered trinitrobenzene ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izz011

    authors: Wardill HR,Choo JM,Dmochowska N,Mavrangelos C,Campaniello MA,Bowen JM,Rogers GB,Hughes PA

    更新日期:2019-06-18 00:00:00

  • Tissue-based Gene Expression as Potential Biomarkers for IBD Course.

    abstract::Inflammatory bowel diseases (IBDs) are highly heterogeneous in disease phenotype, behavior, and response to therapy. Diagnostic and therapeutic decisions in IBD are based primarily on clinical and endoscopic severity and histopathologic analysis of intestinal biopsies. With this approach, however, only a minority of p...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izaa217

    authors: Haberman Y

    更新日期:2020-09-18 00:00:00