miRNA Profiles Colorectal Cancers with Microsatellite Instability Display Unique

Purpose: microRNAs (miRNA) are small noncoding transcripts that play an important role in carcinogenesis. miRNA expression profiles have been shown to discriminate between different types of cancers. The aim of this study was to analyze global miRNA signatures in various groups of colorectal cancers (CRC) based on the presence of microsatellite instability (MSI). Experimental Design:We analyzed genome-widemiRNA expression profiles in 54 CRC tissues [22with Lynch syndrome, 13with sporadicMSI due toMLH1methylation, 19withoutMSI (ormicrosatellite stable, MSS)] and 20 normal colonic tissues by miRNA microarrays. Using an independent set of MSI-positive samples (13 with Lynch syndrome and 20 with sporadic MSI), we developed a miRNA-based predictor to differentiate both types of MSI by quantitative reverse transcriptase PCR. Results: We found that the expression of a subset of nine miRNAs significantly discriminated between tumor and normal colonic mucosa tissues (overall error rate 1⁄4 0.04). More importantly, Lynch syndrome tumors displayed a unique miRNA profile compared with sporadic MSI tumors; miR-622, miR-1238, and miR-192 were the most differentially expressed miRNAs between these two groups. We developed a miRNA-based predictor capable of differentiating between types of MSI in an independent sample set. Conclusions: CRC tissues show distinct miRNA expression profiles compared with normal colonic mucosa. The discovery of unique miRNA expression profiles that can successfully discriminate between Lynch syndrome, sporadicMSI, and sporadicMSS colorectal cancers provides novel insights into the role of miRNAs in colorectal carcinogenesis, which may contribute to the diagnosis, prognosis, and treatment of this disease. Clin Cancer Res; 17(19); 6239–49. 2011 AACR.