Expression And Significance Of HBx Protein In HBV-related Hepatocellular Carcinoma And Paracancerous Tissues And The Impacts On Prognosis

Background:Hepatocellular carcinoma(HCC)is a primary malignant tumor derived from liver cells.It is one of the highest incidence of morbidity and mortality therioma in alimentary system and it has become a universally acknowledged worldwide problem because of its insidious onset,high malignant degree,rapid progress and poor prognosis.Former studies have showed that the principal causes of HCC in China and Southeast Asia were chronic hepatitis B virus(HBV)infection,but the specific mechanisms of development HBV-induced HCC were numerous and complicated.Such as HBV-DNA inserting into human chromosomes randomly,synergetic transactivating functions of HBx extensively,interference regulation of gene transcription,natural mutants of HBV core promoter and transformation regeneration following hepatocyte damage chronically as well as induction formation of tumorigenesis ultimately.In recent years,thanks for the HBx protein has drawn increasingly social attention due to that a wide range of trans-gene activation,DNA damage repairs and epigenetic modifications,and other functions associated with tumorigenesis has been found.In addition,HBx protein binded to the C-terminus of P53 impedes P53 function of apoptosis-inducing,abnormal cells growth interrupting and DNA repairing.On the other hand,HBx anchored to APC competitively displaces ?-catenin from its degradation complex,result in ?-catenin upregulation in the nucleus and the activation of Wnt signaling pathway induced tumorigenesis;and even promote the malignant transformation of ground-glass hepatocytes.Objective:In present research,the expression of HBx protein was detected by immunohistochemistry in HBV-related HCC samples and its corresponding para-tumorous tissues((from the tumor edge < 2cm)).By comparison of its expression,this study was aimed to explore the features of HBx protein in the above tissue as well as the relationships among the clinical factors.Methods:Immunohistochemical staining research methods(Elivision two-step)was used in this study,to detect the expression level of HBx protein in the 40 HCC tissues,corresponding para-tumorous tissues from patients with HBV-related HCC who underwent curative surgical resection performed by single treatment group,and analyzed the relationships between HBx protein and clinical parameters(such as gender,age,TNM stage,HBV-DNA load,AFP,liver cirrhosis,a merger of vascular invasion,tumor infiltrating lymphocytes,Edmondson-Steiner histopathological grading,with or without relapse within 24 months)of the patients with HCC.Results:1.In 40 cases of HBV-related HCC,the expression of HBx protein in the tumorous tissues(40%,16/40)was significantly lower than that of para-tumorous tissues(75%,30/40)(p<0.05).2.In the tissues of para-tumorous,the expression of HBx protein in group which HBV-DNA<500IU/ml(33.33%,2/6)was significantly lower than that of group which HBV-DNA?500IU/ml(82.35%,28/34)(p<0.05).However,there were no significant differences existed in the expression of HBx protein among the clinical parameters of gender,age,cirrhosis of the liver and the serum level of AFP;3.In the tissues of tumorous,the expression of HBx protein in group with vascular invasion(66.67%,8/12)was significantly higher than that of group without vascular invasion(28.57%,8/28)(p<0.05).However,there were no significant differences in the expression of HBx protein among the factors of TNM stage and Edmondson-Steiner histopathology grading;4.In the tissues of para-tumorous,the expression of HBx protein in group with lymphocytic infiltration(86.67%,26/30)was significantly higher than that of group without lymphocytic infiltration(40%,4/10)(p<0.05).In the tissues of tumorous,the expression of HBx protein in group which disease-free survival(DFS)<24M(69.23%,9/13)was significantly higher than that of group which DFS was greater than or equal to 24M(25.93%,7/27)(p<0.05).Conclusion:It is concluded that the expression of HBx protein was higher in para-tumorous tissues than that of tumorous tissues.There are positively correlated with serum HBV-DNA load and lymphocyte infiltration in para-tumorous tissues;while in tumorous tissues,there are negatively correlated with DFS and positively correlated with vascular invasion.In addition,these results may suggest that the high HBx expression in tumorous tissues indicate poor prognosis while in para-tumorous tissues predict a better prognosis.