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

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.

Abbreviations used in this paper: ASCA, anti-Saccharomyces cerevisiae antibodies, AUC, area under the receiver-operating characteristic curve, GRO-α, growth-related oncogene α, IBDU, unclassified inflammatory bowel disease, IBS, irritable bowel syndrome, MMP-7, matrix metalloproteinase 7, pANCA, perinuclear antineutrophil antibodies, qPCR, quantitative polymerase chain reaction, RegIV, regenerating protein IV, ROC, receiver-operating characteristic, SLC, solute carrier, SPAP, small protein associated with PDZ domain–containing protein 1