LAUSR

BACKGROUND Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs are epigenetic regulators that have been involved in the development of UC associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. METHODS In this study, we analyzed the expression of 96 pre-selected microRNAs in human formalin-fixed and paraffin embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia and 12 UC associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual qRT-PCR in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). RESULTS Sixty-four microRNAs were found to be differentially deregulated in the UC associated CRC sequence. Eight of these microRNAs were chosen for further validation. We confirmed miR-31, -106a and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC associated CRC sequence (all P<0.01). Notably, these microRNAs also confirmed to have a significant differential expression compared to sporadic CRC (all P<0.05). CONCLUSIONS UC associated and sporadic CRCs have distinct microRNA expression patterns and some microRNAs indicate early neoplastic progression. TRANSLATIONAL IMPACT The microRNAs identified in this study can guide further large-scale clinical validation studies to improve the early detection of UC associated preneoplastic lesions and cancer.