Background:Preoperative alpha-L-fucosidase (AFU) has been used as a diagnostic biomarker for hepatocellular carcinoma (HCC), but its role as a prognostic predictor after partial hepatectomy has not been well defined. The study aimed to investigate the prognostic significance of preoperative serum AFU for HCC patients after hepatic resection.Methods:A retrospective training data set and a prospective validation data set were used to evaluate the prognosis of HCC after partial hepatectomy. A total of 669 patients with histopathologically confirmed HCC were enrolled. Univariate and multivariate analyses were used to identify the prognostic significance of preoperative serum AFU.Results:The retrospective training data set showed a preoperative AFU>35 u l−1 should be used. The prospective validation data set showed preoperative AFU was an independent prognostic factor of overall survival (OS) (P=0.008; hazard ratio: 2.333; 95% confidence interval: 1.249–4.369). Patients with a preoperative AFU>35 u l−1 had a lower recurrence-free survival rate and an OS rate than those with AFU⩽35 u l−1, and they have a higher tendency to form macrovascular invasion. Furthermore, the prognostic significance of AFU>35 u l−1 could also be applied to patients with alpha-fetoprotein levels of ⩽400 ng ml−1.Conclusions:Preoperative serum AFU is a prognostic predictor of HCC.

BACKGROUND: Portal vein tumour thrombus (PVTT) is highly associated with the progression and metastasis of hepatocellular carcinoma (HCC). However, there are no appropriate cell models of PVTT with which to study the biological and physiological characteristics of PVTT. METHODS: Primary cell culture was performed by the use of a successive xenograft line called PVTT-#1, which was obtained from a 60-year-old male HCC patient accompanied by PVTT. RESULTS: A successive cell line named CSQT-2 was established. The cell line showed aggressive phenotypes in terms of cell growth, survival, migration, xenograft and metastasis. Moreover, an orthotopic transplantation assay showed that PVTT can be generated in nude mice when CSQT-2 cells were inoculated in the liver and that it shows a typical migratory tendency in the vascular branches of portal vein. Moreover, the established CSQT-2 cells also showed varied expression of tumour-initiating cell (TIC) markers such as CD133, CD90 and EpCAM. CONCLUSION: Establishment of CSQT-2 may provide a suitable model with which to investigate the molecular mechanisms of PVTT-related HCC.

Hepatocarcinogenesis is a complex process involving chronic liver injury, inflammation, unregulated wound healing, subsequent fibrosis and carcinogenesis. To decipher the molecular mechanism underlying transition from chronic liver injury to dysplasia, we investigated the oncogenic role of gankyrin (PSMD10 or p28GANK) during malignant transformation in a transgenic mouse model. Here, we find that gankyrin increased in patients with cirrhosis. In addition to more severe liver fibrosis and tumorigenesis after DEN plus CCl4 treatment, hepatocyte-specific gankyrin-overexpressing mice (gankyrinhep) exhibited malignant transformation from liver fibrosis to tumors even under single CCl4 administration, whereas wild-type mice merely experienced fibrosis. Consistently, enhanced hepatic injury, severe inflammation and strengthened compensatory proliferation occurred in gankyrinhep mice during CCl4 performance. This correlated with augmented expressions of cell cycle-related genes and abnormal activation of Rac1/c-jun N-terminal kinase (JNK). Pharmacological inhibition of the Rac1/JNK pathway attenuated hepatic fibrosis and prevented CCl4-induced carcinogenesis in gankyrinhep mice. Together, these findings suggest that gankyrin promotes liver fibrosis/cirrhosis progression into hepatocarcinoma relying on a persistent liver injury and inflammatory microenvironment. Blockade of Rac1/JNK activation impeded gankyrin-mediated hepatocytic malignant transformation, indicating the combined inhibition of gankyrin and Rac1/JNK as a potential prevention mechanism for cirrhosis transition.