Gastroenterology

Gastroenterology

Volume 134, Issue 7, June 2008, Pages 1869-1881
Gastroenterology

Clinical–Alimentary Tract
Multigene Analysis Can Discriminate Between Ulcerative Colitis, Crohn's Disease, and Irritable Bowel Syndrome

https://doi.org/10.1053/j.gastro.2008.02.083Get rights and content

Background & Aims: Inflammatory bowel diseases (IBDs) and the irritable bowel syndrome (IBS) are heterogeneous disorders of the gastrointestinal tract and can profoundly affect the quality of life. Because many of the symptoms of IBD are similar to those of IBS, the former may be misdiagnosed. In addition, the 2 major forms of IBD, ulcerative colitis (UC) and Crohn's disease (CD), have overlapping nonspecific, pathologic features leading to difficulties in assessing colonic inflammation and hence the term IBD unclassified has been proposed. The aim of this study was to identify and assess the utility of a certain set of marker genes that could help to distinguish IBS from IBD, and further to discriminate between UC and CD. Methods: Subtractive suppression hybridization was used to identify IBD-specific genes in colonic mucosal biopsy specimens. In quantitative polymerase chain reaction experiments, the differential expressions of identified genes then were analyzed using a classification algorithm and the possible clinical value of these marker genes was evaluated in a total of 301 patients in 3 stepwise studies. Results: Seven marker genes were identified as differentially expressed in IBD, making it possible to discriminate between patients suffering from UC, CD, or IBS with area under the receiver-operating characteristic curves ranging from 0.915 to 0.999 (P < .0001) using the clinical diagnosis as gold standard. Conclusions: Expression profiling of relevant marker genes in colonic biopsy specimens from patients with IBD/IBS-like symptoms may enable swift and reliable determination of diagnosis, ultimately improving disease management.

Section snippets

Pilot study

Biopsy samples were collected in a prospective manner at the IBD-unit at Sophiahemmet (Stockholm, Sweden). Fifty-five IBD patients (23 women and 32 men) with a mean age of 44.6 years (range, 19–76 y), and a mean disease duration of 4.5 years (range, 1 mo to 18 y) and 8 IBS patients were included.

Retrospective study

Complementary DNA (cDNA) samples derived from mucosal biopsy samples of 55 IBD and 88 non-IBD patients were used (65 women and 78 men), collected at the Sahlgrenska University Hospital (Gothenburg,

Screening for IBD-Specific Genes

To identify IBD-specific genes we used a screening procedure with the subtractive suppression hybridization method, which enables the enrichment and isolation of dysregulated genes by comparing 2 cDNA populations,10, 12 in this case inflamed and noninflamed biopsy samples of 8 UC patients. For each patient, 2 subtractions were performed, enabling the isolation of both up-regulated and down-regulated genes specific to the inflamed biopsy specimens (Figure 1A). This resulted in the identification

Discussion

Gastrointestinal disorders such as IBD can dramatically affect quality of life,17 and the diagnosis can be a challenging process. In up to 30% of patients, only a temporary diagnosis of IBDU can be made. An early and accurate assessment of the diagnosis could have important clinical implications in the choice of medical treatment and for surgery considerations (eg, when colectomy, and later construction of a pelvic pouch, will be contemplated). Genetic and serologic studies have shown

References (43)

  • J. Satsangi et al.

    The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications

    Gut

    (2006)
  • G.T. Martland et al.

    Indeterminate colitis: definition, diagnosis, implications and a plea for nosological sanity

    Histopathology

    (2007)
  • P.J. Mitchell et al.

    Indeterminate colitis

    Tech Coloprocol

    (2007)
  • N.J. Talley

    Irritable bowel syndrome

    Intern Med J

    (2006)
  • D.H. Bruining et al.

    Evolving diagnostic strategies for inflammatory bowel disease

    Curr Gastroenterol Rep

    (2006)
  • X. Bossuyt

    Serologic markers in inflammatory bowel disease

    Clin Chem

    (2006)
  • K.A. Papadakis et al.

    Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations

    Inflamm Bowel Dis

    (2007)
  • M. Ferrante et al.

    New serological markers in inflammatory bowel disease are associated with complicated disease behaviour

    Gut

    (2007)
  • O.D. von Stein

    Isolation of differentially expressed genes through subtractive suppression hybridization

    Methods Mol Biol

    (2001)
  • C.F. Flach et al.

    Detection of elafin as candidate biomarker for ulcerative colitis by whole genome microarray screening

    Inflamm Bowel Dis

    (2006)
  • L. Diatchenko et al.

    Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries

    Proc Natl Acad Sci U S A

    (1996)
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    Supported by a grant from the foundation for clinical research at Sophiahemmet, Stockholm, Sweden.

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