In our population, it also seems to have a greater influence on treatment response. IL28B’s mechanism of action is likely effected through ISG expression. These results indicate that patient’s native IL28B genotype has a greater influence than donor genotype on relevant ISG expression, and consequently on treatment response. Disclosures: Richard Gilroy – Advisory Committees

or Review Panels: FDA GIDAC; Speaking and Teaching: Salix, Vertex, Gilead The following people have nothing to disclose: Zoe Raglow, Chuanghong Wu, Winston PKC inhibitor Dunn, Yu-Jui Y. Wan BACKGROUND & AIMS MicroRNAs (miRNAs) are an important class of small non-coding RNA molecules that bind to their complementary sequence on their target mRNAs, resulting in translational repression. MiRNAs play major

roles in development, metabolism, infection, and cancer. The diagnosis of cholangiocarcinoma is sometimes difficult due to the lack of a specific tumor marker and limited sampling for histological evaluation. In this study, we analyzed miRNA expression in bile to identify predictive miRNAs for hepatobiliary malignancy. METHODS MiRNAs were obtained from bile samples taken from 25 patients with benign hepatobiliary disease and 34 patients with malignant hepatobiliary disease, including cholangiocarcinoma and gallbladder cancer. Expression of 328 miRNAs was determined with the TaqMan real-time PCR detection system using a MicroRNA Assays Human Panel. MiRNAs were functionally ZD1839 in vitro evaluated in cholangiocarcinoma cell lines (Huh28, Hucct1, and KMBC) following the overexpression or knocking down of specific miRNAs using mimic-miRNA or anti-miRNA. RESULTS Among the 328 miRNAs tested, 16 were differentially expressed between the bile of patients with malignant hepatobiliary disease and those

with benign hepatobiliary to disease (p<0. 05). From these 16 miRNAs, we focused on the two—miR-451 and miR-486—that were most significantly increased in malignant hepatobiliary disease. The area under the curve of the receiver operating characteristic curve for the prediction of malignant hepatobiliary disease using these miRNAs was 0. 85, which was equivalent to that of the tumor marker CA19-9. Univariate analysis using multiple clinical parameters, including tumor markers (CEA and CA19-9) and a liver function test, revealed serum ALT and T-Bil, miR-451, and miR-486 as significant variables. Multivariate analysis identified CEA, CA19-9, and miR-486 as significant variables. Functional analysis of these miRNAs showed that miR-451 had tumor suppressive and anti-inflammatory properties by decreasing the expression of PDGFRα, KRT7, IL1, and IL6, while miR486 was tumorigenic by increasing the expression of PDGFRα, N-cadherin, and p38MAPK. CONCLUSIONS We identified two predictive miRNAs, miR-451 and −486, in bile for the diagnosis of malignant hepatobiliary disease.