Differential expression of SEMA7A in the liver, which occurs during fibrogenesis, may potentially explain the

increased risk of HCC development in the course of cirrhosis. Disclosures: The following people have nothing to disclose: Samuele De Minicis, Chiara Rychlicki, Laura Agostinelli, Cinzia Candelaresi, Luciano Trozzi, Stefania Saccomanno, Eleonora Mingarelli, Marco Marzioni, Antonio Benedetti, Gianluca Svegliati-Baroni Vascular invasion has been known to be a strong p38 MAPK phosphorylation predictor of hepatocellular carcinoma (HCC) recurrence after liver transplant, but clinically reliable molecular markers for vascular invasion are still not available yet. Here we report a miRNA signature that can distinguish recurrent HCC with vascular invasion from recurrent HCC without vascular invasion. We examined vascular invasion on 124 HCC tumor nodules from a cohort of 77 HCC patients, 45 of whom had recurrent HCC within 3 years of transplant. IWR-1 purchase We performed miRNA expression profiling on all nodules using miRNA microarrays. High value miRNA candidates (most statistically significant and present in the HCC recurrence with macrovascular invasion) were then be validated by qPCR verification. We found that 1 3 miRNAs were differentially expressed with at least 2 fold expression change with p<0.05 (12

downregulated: miR-22, miR-29a, miR-30a, miR-34a, miR-99a, miR-100, miR-126, miR-192, miR-194, miR-195, miR-199a, and miR-497, and 1 upregulated: miR-494). Hierarchical clustering of miRNAs versus patients clearly shows that these miRNAs significantly distinguish patients with and without HCC macrovascular invasion. Further analyses of these miRNAs demonstrates that most of 12 down-regulated

miRNAs can inhibit HCC cell survival, proliferation, MCE公司 and angiogenesis via suppressing IGF, WNT, and VEGF signaling pathways, while the up-regulated miR-494 is a convergent downstream of oncogenic transcriptional factors such as H-Ras, c-Jun, and E2F. Our study discovers a miRNA signature distinguishing between recurrent HCC with and without macrovascular invasion. This miRNA signature may serve as a prognostic biomarker and also help direct therapeutic interventions for HCC. Disclosures: Christa L. Whitney-Miller – Grant/Research Support: Genentech The following people have nothing to disclose: KuangHsiang Chuang, Mark S. Orloff, Matthew N. McCall, Anthony Almudevar, Christopher T. Barry Introduction Sorafenib, a multi-tyrosine kinase inhibitor, is the only FDA approved chemotherapeutic agent for metastatic hepatocellular carcinoma (HCC). We have previously shown that triptolide enhances apoptosis in HuH-7 HCC cells. In this study, we examined the effects of these agents and their combination on HCC in vitro and in vivo. Methods HuH-7 cells were treated with triptolide (T – 50 nM), sorafenib (S – 1.