6-8 Nevertheless, correlations are not always found between tumor stage and the actual prognosis, and this phenomenon is more common in patients with early HCC than in those with advanced HCC. Considering that HCC is increasingly diagnosed and resected at an early stage and that current staging systems have some limitations in the prognostic evaluation of early HCC,4, 9, 10 efforts have been made to investigate prognostic molecules.11-13 To date, no easily measurable biomarker that has strong correlations with

clinical outcomes has been identified. Human aspartyl-(asparaginyl)-β-hydroxylase (AAH) is abundantly expressed in proliferating trophoblastic cells of the placenta and is rarely expressed in normal adult tissues.14 Overexpression of AAH can promote the malignant transformation of biliary epithelial cells, enhance the metastasis of cholangiocarcinoma cells,14-17 AZD8055 nmr and increase the mobility of neuroblastoma.18 Wands and colleagues14, 19 have reported that AAH is highly expressed in HCCs and that overexpression of AAH significantly increases motility and invasiveness of HepG2 and Huh-7 cells.20, 21 Our previous study also showed enhanced AAH immunostaining in HCC when compared with that in nontumorous tissue, which was associated with poor differentiation of HCC cells.22 However, the click here significance of AAH expression level in the prognostic evaluation of patients undergoing surgical resections

has not been reported. The purpose of this prospective study was to examine whether AAH expression level is an effective prognostic factor for HCC patients who undergo hepatectomy. selleck chemicals llc Differential expression levels of AAH in HCCs and nontumorous tissues were analyzed through hybridization with complementary DNA (cDNA) microarray, reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemical staining in tissue microarray (TMA). We found that AAH expression level in tumor tissue was well-correlated with multiple malignant clinico-pathological

characteristics and was strongly associated with tumor recurrence and patient survival. Moreover, AAH overexpression predicted a worse surgical outcome in patients with early stage HCC according to Barcelona Clinic Liver Cancer (BCLC) staging classification. AAH, aspartyl-(asparaginyl)-β-hydroxylase; AFP, AFP, α-fetoprotein; BCLC, Barcelona Clinic Liver Cancer; cDNA, complementary DNA; CI, confidence interval; HCC, hepatocellular carcinoma; HR, hazard ratio; mRNA, messenger RNA; PVTT, portal vein tumor thrombosis; RT-PCR, reverse-transcription polymerase chain reaction; TMA, tissue microarray; TTR, time to recurrence. A total of 281 adult patients with HCC undergoing hepatectomy by three independent surgical teams at Eastern Hepatobiliary Surgery Hospital between January 1 and June 30, 2004, were enrolled in the study. The preoperative clinical diagnosis of HCC met the diagnostic criteria of the American Association for the Study of Liver Diseases.