miRNA profiles of these samples brought two important insights to the understanding of hepatocarcinogenesis. First, we found that

miRNA deregulation is an early event in which discernible difference was observed between miRNA profiles of primary HCCs and nontumorous liver through clustering analysis. However, no major change was observed between the miRNA profiles of primary HCCs and venous metastases. Second, unlike other cancers, no global miRNA down-regulation was detected LDK378 price in primary HCCs. Instead, marked global miRNA down-regulation was detected in venous metastases, and this global miRNA down-regulation could exacerbate the preexisting miRNA deregulation in primary HCCs and facilitate metastasis formation. HBV, hepatitis B virus; HCC, hepatocellular carcinoma; miRNA, Talazoparib solubility dmso microRNA; PCR, polymerase chain reaction; snoRNA, small nucleolar RNA; TLDA, TaqMan Low-Density Array. Twenty advanced HCC cases with intrahepatic metastasis as diagnosed with the presence of venous thrombi were selected from a large cohort of approximately 400 HCC patients who underwent curative surgical resection at Queen Mary Hospital, Hong Kong, between 1999 and 2009. Formalin-fixed and paraffin-embedded sections were retrieved from these cases, and the presence of venous thrombi was reviewed by an experienced liver pathologist (IOLN). In our

center, HCCs with gross tumor thrombosis in the portal vein are often inoperable. We therefore selected only those cases in which the venous thrombi were large 上海皓元医药股份有限公司 enough for microdissection. Twenty HCC cases with medium-sized (3-10 mm) HCC thrombi were selected for this study. All patients were of Chinese origin, with a mean age of 51.5 years; 19 were male and one was female. Eighteen patients had chronic hepatitis B virus (HBV) infection, as shown by the positive serum HBV surface antigen status, and the remaining two patients had chronic hepatitis C viral (HCV) infection, as shown by the positive serum anti-HCV status. There were no patients with both HBV and HCV infection. Liver cirrhosis

was present in 13 patients. The demographic data and clinicopathological features of the patients are described in Supporting Table 1. Use of human samples was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster. Paraffin sections were cut at a thickness of 4 μm, dewaxed, rehydrated, and lightly stained with hematoxylin. Nontumorous livers and their corresponding primary HCC tissues and venous thrombi were examined and microdissected with a 25-gauge needle under a dissecting microscope as described. 11, 12 Four to eight consecutive tissue sections were cut in each case to obtain enough microdissection material for further evaluation. miRNA extraction was performed with an miRNeasy FFPE kit (Qiagen, Valencia, CA).