Novel plasma microRNA biomarkers for the identification of colitis-associated carcinoma

Abstract

BackgroundUlcerative colitis is an established risk factor for colorectal cancer, also known as colitis-associated cancer. Existing colonoscopic-based surveillance has many disadvantages, so a new accurate, efficient, cost-effective screening test is needed. MicroRNAs (miRNAs) regulate gene expression and are dysregulated in a range of diseases, including ulcerative colitis and colorectal cancer. This study aimed to establish the miRNAs associated with colitis-associated cancer. MethodsBlood samples were collected from 45 adult patients undergoing colonoscopic screening for ulcerative colitis at the Leicester General Hospital, Leicester, UK. Pool A and B TaqMan Array 384-well cards were used to quantify the expression of 754 miRNAs in the circulating plasma. 28 high priority miRNA candidates showing abnormal expression were validated with real-time quantitative PCR. FindingsPatients were allocated to three disease groups (ulcerative colitis, n=37; dysplasia, n=2; colitis-associated cancer, n=6). Analysis of variance was used to assess differences between the groups. miR-375 was significantly upregulated in the colitis-associated cancer cohort (p=0·0061) compared with active ulcerative colitis. Combining several miRNAs in a panel increased the capacity of the test to distinguish between colitis-associated cancer and different ulcerative colitis activity states. InterpretationOur study suggests that miRNAs have the potential to act as blood-based biomarkers to monitor the activity and progression of disease in patients with ulcerative colitis. FundingRoyal College of Surgeons of England.