Blood microRNA (miRNA) Expression Patterns Can Identify Inflammatory Bowel Disease (IBD) Patients with Dysplasia and Cancer: 2011 ACG Presidential Poster: 1212

Purpose: Patients with longstanding and extensive IBD have an increased risk of developing dysplasia (D) and cancer (C). MicroRNAs (miRNAs) are a class of small noncoding RNA involved in post-transcriptional regulation of gene expression that play important roles in cell proliferation, apoptosis and differentiation. More than 50% of human miRNA genes are located at sites involved in cancer suggesting their role in tumorigenesis. MiRNA have been found to be differently expressed in normal and tumor tissues. The aim of this study is to categorize serum miRNA profiles in IBD patients with and without dysplasia or cancer. Methods: IBD patients (2 with IBD/D, 2 with IBD/C, 6 IBD controls without D/C) and 2 non-IBD sporadic C patients were identified at the Boston Medical Center IBD Center. MiRNA were extracted from blood using Qiagen PAXgene miRNA kit and screened using the SmartChip Human MicroRNA Panel (Wafergen Biosystems) that consist of 1200 microRNA specific assays. A pool of 15 positive miRNAs down-regulated at least two fold was selected for additional study; every assay was subsequently confirmed using individual TaqMan miRNA assays (Applied Biosystems). The data were normalized using U6 SnRNA. Results: A set of 15 miRNA were identified as down-regulated in the IBD/D and IBD/C patients; hsa-miR-16, hsa-miR-15b, hsa-miR-15a. hsa-let-7f, hsamiR-30b, hsa-miR-649, hsa-miR-575, hsa-miR-106a, hsa-let-7g, hsa-miR-223, hsa-miR-17, hsa-miR-652, hsa-miR-1287, hsa-miR-1229 and hsa-miR-21. To assess the specificity of this 15 miRNA pool, an additional 12 IBD controls were tested. Six IBD samples showed no expression differences while the remaining 6 samples had only 1 out of the 15 miRNA down-regulated. No differences were observed between UC and CD patients. The two non IBD sporadic colorectal cancer patients used in the initial screening studies were confirmed to have no decrease in expression of these 15 miRNAs. Six samples from four IBD/D patients that included two samples initially screened were also tested with the 15 miRNA set. Three of these samples showed a difference of expression profile for at least 3 miRNAs out of 15. In IBD/C patients, 2 of 3 samples tested were also identified has having 3 or more miRNAs down regulated. Conclusion: We have identified a pool of 15 miRNA that can identify IBD patients with dysplasia or cancer. None of the IBD control patients displayed more than one down regulated miRNA. These preliminary data suggest that when using this set of 15 miRNA, IBD patients with 3 or more down-regulated miRNAs should be suspected as having dysplasia or cancer. More samples will be needed to be able to fully assess the predictive value of this set 15 miRNA biomarkers. Disclosure: Dr. Farraye - Research Support and Advisory Board, Prometheus Labs. Michelle Brown, BA, Sharat Singh, PhD and Fred Princen, PhD - employees of Prometheus Labs. This research was supported by an industry grant from Prometheus Therapeutics and Diagnostics.