miRNA Expression Pattern in Indeterminate Colitis
Jingmei Lin, Qi Cao, Jianjun Zhang, Yong Li, John R Goldblum, Mary P Bronner. Indiana University School of Medicine, Indianapolis, IN; University of Michigan, Ann Arbor, MI; Cleveland Clinic, Cleveland, OH; University of Utah, Salt Lake City, UT
Background: A diagnosis of idiopathic inflammatory bowel disease (IBD) is rendered by synthesizing clinical, radiographic, endoscopic, and histologic information. While most IBD cases can be specifically classified as either ulcerative colitis (UC) or Crohns disease (CD), 5-10% of patients have equivocal features, falling into the category of IBD indeterminate type or indeterminate colitis (IC). The molecular mechanism underlying IC is unknown. Herein, we explored the microRNA (miRNA) expression patterns in patients with IC.
Design: Frozen colon tissues from the distal part of the colectomy of 16 IC patients, 11 CD patients, 12 UC patients, and a control group of 11 patients with diverticular disease were identified. Total RNA was extracted and qRT-PCR was performed using five pairs of miRNA primers (miR-19b, miR-23b, miR-106a, miR-191, and miR-629). The level of each miRNA in the study groups was normalized to the mean value of the control. The general liner multiple regression analysis and the discriminant analysis were performed to evaluate the variance of miRNA expression and the capacity of five markers, as a whole, to differentiate the diseases of interest, respectively.
Results: There was significant difference in the expression of miR-19b, miR-106a and miR-629 between UC and CD groups (P<0.05). The expression level of all five miRNAs was statistically different between IC and CD groups (P<0.05), respectively, but no significant difference existed between IC and UC groups. Discriminant analysis demonstrated that, as a whole, five miRNAs have a good capacity in distinguishing CD-like pattern from non-CD-like pattern. Nine of 14 CD patients (64.3%) showed CD-like miRNA pattern compared to 0% of UC patients. Among the 16 IC patients, definitive diagnosis of UC had been reached for four patients (25%) and all of them had UC-like miRNA pattern. Among the 12 patients whose diagnosis remained IC during follow-up, one showed CD-like pattern but the other 11 did not.
Conclusions: miRNA expression pattern in IC, as a whole, is similar to that of UC, not CD. Our study provides the molecular evidence to believe that most IC cases are UC. miRNA may be a useful diagnostic and prognostic marker to distinguish rare IC patients that will prove to have CD.
Tuesday, March 20, 2012 9:15 AM
Platform Session: Section D, Tuesday Morning