Our study aimed to investigate the short-term efficacy and long-term prognosis of liver failure patients caused by hepatitis B after a single transplantation with autologous marrow mesenchymal stem cells (MMSCs). A total of 527 inpatients with liver failure caused by hepatitis B were recruited and received the same medical treatments, among whom 53 patients underwent a single transplantation with autologous MMSCs. A total of 105 patients matched for age, sex, and biochemical indexes, including alanine aminotransferase (ALT), albumin, total bilirubin (TBIL), prothrombin time (PT), and Model for End-Stage Liver Disease (MELD), comprised the control group. A total of 120 mL of bone marrow was obtained from each patient and then diluted and separated. Then, the MMSC suspension was slowly transfused into the liver through the proper hepatic artery. The success rate of transplantation was 100%, without serious side effects or complications. Levels of ALB, TBIL, and PT and MELD score of patients in the transplantation group were markedly improved from 2-3 weeks after transplantation, compared with those in the control group. At 192 weeks of follow-up, there were no dramatic differences in incidence of hepatocellular carcinoma (HCC) or mortality between the two groups. Additionally, there were no significant differences in the incidence of HCC or mortality between patients with and without cirrhosis in the transplantation group. Conclusion: Autologous MMSC transplantation is safe for liver failure patients caused by chronic hepatitis B. Short-term efficacy was favorable, but long-term outcomes were not markedly improved. In respect to several parameters, this method is preferable for patients with liver cirrhosis and may have potential for reducing their incidence of HCC and mortality. (HEPATOLOGY 2011;54:820-828) H epatitis B is a major global health problem and the most serious type of viral hepatitis. It is one of the primary causes of liver cirrhosis, liver failure and is one of the major risk factors of hepatocellular carcinoma (HCC), with approximately 350 million people infected worldwide.1 The disease is particularly serious in some developing countries, and new, effective therapies are essential, in addition to current medical, antiviral, and immunomodulation treatments and liver transplantation.

It has been reported that the transcription factor activating enhancer-binding protein 4 (TFAP4) is upregulated and associated with an aggressive phenotype in several cancers. However, the precise mechanisms underlying the oncogenic role of TFAP4 remain largely unknown.Methods: TFAP4 expression levels in hepatocellular carcinoma (HCC) cells and tissues were detected by quantitative real-time PCR (qPCR) and immunohistochemistry (IHC). In vitro and in vivo assays were performed to investigate the oncogenic function of TFAP4 in the tumor-initiating cell (TIC)-like phenotype and the tumorigenic capability of HCC cells. Luciferase reporter and chromatin immunoprecipitation (ChIP)-qPCR assays were performed to determine the underlying mechanism of TFAP4-mediated HCC aggressiveness.Results: TFAP4 was markedly upregulated in human HCC, and was associated with significantly poorer overall and relapse-free survival in patients with HCC. Furthermore, we found that overexpression of TFAP4 significantly enhanced, whereas silencing TFAP4 inhibited, the tumor sphere formation ability and proportion of side-population cells in HCC cells in vitro, and ectopic TFAP4 enhanced the tumorigenicity of HCC cells in vivo. Mechanistically, we demonstrated that TFAP4 played an important role in activating Wnt/β-catenin signaling by directly binding to the promoters of DVL1 (dishevelled segment polarity protein 1) and LEF1 (lymphoid enhancer binding factor 1).Conclusions: Our results provide new insight into the mechanisms underlying hyperactivation of the Wnt/β-catenin pathway in HCC, as well the oncogenic ability of TFAP4 to enhance the tumor-forming ability of HCC cells.

Chromobox (CBX) proteins are important components of epigenetic regulation complexes known to play key roles in hepatocellular carcinoma (HCC). Little is known about the function of distinct CBXs in HCC. To address this issue, the study investigated the roles of CBXs in the prognosis of HCC using ONCOMINE, UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, c-BioPortal databases. Over expressions of 8 CBXs members were found to be significantly associated with clinical cancer stages and pathological tumor grades in HCC patients. Besides, higher mRNA expressions of CBX1/2/3/6/8 were found to be significantly associated with shorter overall survival (OS) in HCC patients, while higher mRNA expression of CBX7 was associated with favorable OS. Multivariate analysis also showed that high mRNA expressions of CBX1/2/3/6/8 were independent prognostic factors for shorter OS of HCC patients. Moreover, high mutation rate of CBXs (51%) was also observed in HCC patients, and genetic alteration in CBXs was associated with shorter OS and disease-free survival (DFS) in HCC patients. Taken together, these results indicated that CBX1/2/3/6/8 could be prognostic biomarkers for survivals of HCC patients.

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BackgroundThe La-related protein 1 (LARP1) has been found to be a RNA binding protein and was related to spermatogenesis, embryogenesis and cell-cycle progression. The aim of this study was to investigate the prognostic value of LARP1 in hepatocellular carcinoma (HCC).MethodsLARP1 expression was examined in 15 HCC cell lines and 272 clinical specimens using real-time PCR, immunohistochemistry (IHC) and western blot analysis (WB). LARP1 expression was also studied in 6 paired HCC lesions and the adjacent non-cancerous tissue samples. Statistical analyses were applied to derive association between LARP1 expression scores and clinical characters as well as patient survival.ResultsmRNA and protein levels of LARP1 were higher in HCC cell lines and HCC lesions than in normal liver epithelial cells and the paired adjacent noncancerous tissues. LARP1 expression was correlated to survival time, vital status, tumor size and Child-Pugh score. Overall survival analysis showed HCC patients with high LARP1 expression level had lower survival rate (P < 0.01). Importantly, this correlation remained significant in patients with early-stage HCC or with normal serum AFP level.ConclusionsLARP1 protein may represent a promising biomarker for predicting the prognosis of HCC, including in early-stage and AFP-normal patients.