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BACKGROUND The aim of this study was to compare the expression levels of mRNA of the B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) and the WW domain-containing oxidoreductase (WWOX) genes and their protein products in tissues from patients with liver cancer with normal liver tissues from patients without liver cancer. MATERIAL AND METHODS The liver cancer group (N=56) included patients with available tissue samples of histologically confirmed liver cancer. The control group (N=24) included histologically confirmed normal liver tissue samples. Immunofluorescence staining and Western blot were used to detect and compare protein expression of Bmi-1 and WWOX in liver tissues in the liver cancer group and the control group. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect and compare mRNA expression of BMI-1 and WWOX in liver tissues in the liver cancer group and the control group. Expression levels of the protein and mRNA levels and the clinicopathological features including patient prognosis in liver cancer were evaluated statistically using analysis of variance (ANOVA). RESULTS There were significant differences in the expression levels of protein and mRNA of BMI-1 and WWOX between the liver cancer group and the control group. BMI-1 mRNA and protein expression were significantly increased, and WWOX mRNA and protein expression were significantly reduced in liver cancer tissue, compared with normal liver tissue (p

As a conserved cellular stress response, autophagy has recently been demonstrated to be involved in the pathogenesis of several human cancers. Beclin-1 is an important autophagy gene that is abnormally expressed in a variety of human cancers. In this study, we investigated the expression of Beclin-1 in Hepatocellular Carcinoma (HCC).A total of 83 patients with primary HCC were enrolled in this study. The expression of Beclin-1, PCNA, NET-1, Bcl-2, and Bax was measured in tissue microarray, including 83 cases of HCC and 46 adjacent non-tumor liver tissues. The association of the expression of Beclin-1 with clinicopathological features as well as PCNA, NET-1, Bcl-2, and Bax were analyzed.The positive rate of Beclin-1 in HCC tissues was significantly lower than that in adjacent tissues (x2 = 4.013, p=0.012). Beclin-1 expression in HCC tissues was negatively correlated with the expression of PCNA, NET-1, and anti-apoptotic protein Bcl-2, but positively correlated with pro-apoptotic protein Bax expression. Meanwhile, Beclin-1 expression was negatively correlated with HCC Edmondson grading (p=0.0058). Furthermore, Beclin-1 expression was significantly lower in HCC patients with liver cirrhosis (p=0.029) or vascular invasion (p=0.011) than those in HCC patients without cirrhosis or vascular invasion.Decreased expression of Beclin-1 was observed in HCC tissues and negatively correlated with HCC Edmondson grading, suggesting that Beclin-1 might be a valuable prognostic indicator for HCC.

In the present study, the inhibitory effect of transmembrane Tim-3 on hepatocellular carcinoma Hepa1-6 cells and the potential application of Tim-3 on immune system of Institute of Cancer Research (ICR) mice loaded with Hepa1-6 hepatocellular carcinoma was investigated. The animal model was established via inoculation of Hepa1-6 hepatocarcinoma cells at the hind thigh of ICR mice. Recombinant vector plasmids were transfected at the same site for gene therapy by injection to observe the inhibitory effect of Tim-3 on tumor growth. A panel of genes from tumor tissues at various time intervals was analyzed by reverse transcription-polymerase chain reaction. Flow cytometry was used to evaluate the proliferation and cytotoxicity of splenocytes after Tim-3 transfection. Synergistic effects of Tim-3 with tumor abnormal protein-1 (TAP1) was also studied. It was revealed that the growth of tumor was significantly suppressed after the transfection of Tim-3. In the presence of Tim-3, the proliferation of splenocytes and cytolysis in the early phase of tumor development was significantly enhanced, and this antitumor effect was further improved by the synergistic effect of Tim-3 with TAP1. Therefore, the membrane-type Tim-3 may behave as an effective immunoregulator to enhance antitumor immune responses. Furthermore the present findings suggest that antitumor immunity was improved by the combined effect of Tim-3 and TAP1.

Chronic hepatitis B (CHB) is one of the most common infectious disease worldwide and a leading cause of death. Hepatitis B surface antigen (HBsAg) has previously been proven to be a steady biomarker that may be used to predict clinical outcomes. The amount of circulating HBsAg has been reported to reflect the number of infected hepatocytes. An advantage of pegylated interferon alpha (peg-IFN-α) is that as a finite course of therapy, it can potentially lead to sustained disease remission in subsequent decades. HBsAg seroclearance can reportedly be achieved in some hepatitis B patients treated with peg-IFN-α; this is a major advantage of IFN-α, as compared with nucleoside analogue treatment. In the present study, a random phage display peptide library was used to screen for potential serum peptide biomarkers in predicting which patients with CHB would exhibit HBsAg seroclearance, following 48 weeks of peg-IFN-α therapy. A total of 30 patients with CHB who achieved HBsAg seroclearance following peg-IFN-α therapy and an additional 30 age-, gender-, hepatitis B e antigen (HBeAg) status- and hepatitis B virus genotype-matched patients with CHB without HBsAg seroclearance following peg-IFN-α therapy, were enrolled as a discovery cohort. In the discovery/screening phase, 17/20 of the randomly selected phage clones, exhibited a specific reaction with purified sera immunoglobulin G from the HBsAg clearance group, and 13/17 positive phage clones came from the same phage clone, with the inserted peptide sequence ETCRASCINESA (named IFNC1). In the validation phase, phage-ELISA results showed that the positive reaction rate of the IFNC1 peptide phage clone was 92.0% with the HBsAg seroclearance group (n=50), which was significantly higher, as compared with the randomly selected HBsAg non-clearance group (12.0%, n=50) and the healthy control group (8.0%, n=50). In conclusion, the newly identified mimic peptide IFNC1 showed a high predictive validity HBsAg seroclearance in patients with CHB, following peg-IFN-α therapy. Therefore IFNC1 may be a potential serum biomarker, which could be used to predict the treatment outcomes of peg-IFN-α therapy.

BackgroundHuman leukocyte antigen DP (HLA-DP) locus has been reported to be associated with hepatitis B virus (HBV) infection in populations of Japan and Thailand. We aimed to examine whether the association can be replicated in Han Chinese populations.Methodology/principal findingsTwo HLA-DP variants rs2395309 and rs9277535 (the most strongly associated SNPs from each HLA-DP locus) were genotyped in three independent Han cohorts consisting of 2 805 cases and 1 796 controls. By using logistic regression analysis, these two SNPs in the HLA-DPA1 and HLA-DPB1 genes were significantly associated with HBV infection in Han Chinese populations (P = 0.021∼3.36×10(-8) at rs2395309; P = 8.37×10(-3)∼2.68×10(-10) at rs9277535). In addition, the genotype distributions of both sites (rs2395309 and rs9277535) were clearly different between southern and northern Chinese population (P = 8.95×10(-5) at rs2395309; P = 1.64×10(-9) at rs9277535). By using asymptomatic HBV carrier as control group, our study showed that there were no associations of two HLA-DP variants with HBV progression (P = 0.305∼0.822 and 0.163∼0.881 in southern Chinese population, respectively; P = 0.097∼0.697 and 0.198∼0.615 in northern Chinese population, respectively).ConclusionsOur results confirmed that two SNPs (rs2395309 and rs9277535) in the HLA-DP loci were strongly associated with HBV infection in southern and northern Han Chinese populations, but not with HBV progression.