| Objectives: To clarify their roles and correlation of HBV genes product, nucleartranscription factor-κB (NF-κB), cyclinD1, Bcl-2 and Heat shock protein70 (HSP70)in the initiation and development of hepatocellular carcinoma (HCC), their proteinexpression level was detected in hepatitis-related HCC group, posthepatitic cirrhosisgroup and control group.Methods: Tissue array was made with 152 cases patients with hepatitis-related HCCand 78 cases patients with posthepatitic cirrhosis after reassessing by pathologists.Four spots in slide were taken out to make the tissue array for each case.Immunohistochemical staining was performed on the slides after HE staining.Staining Index (SI) was used to assess the expression of each factor according toMattem Method. The Statistical Package for Social Sciences (SPSS) version 11.5 wasused for all calculations. The significance level was set at 0.05 for each analysis.Results:1. The expression level of HBcAg, HBx protein, NF-κB, cyclinD1 and HSP70 washigher in HCC group than that in posthepatitic cirrhosis group and control group(P＜0.01), which means they play an important role in the malignant change of HCC.The expression level of Bcl-2 was lower in HCC group than that in posthepatiticcirrhosis group and control group (P＜0.01), which means it can be against apoptosisin precancerous lesions of HCC and maybe an early molecular event. The expressionlevel of HBsAg was lower in HCC group than that in posthepatitic cirrhosis group(P＜0.05), and HBsAg only correlated with the HSP70 (P＜0.01), which means HBsAg has little relationship with the initiation of HCC.2. The expression level of HBx had a positive correlation with the expression ofcyclinD1, NF-κB, cyclinD1, Bcl-2 and HSP70 (P＜0.01), besides correlated with theexpression of HBcAg and HBsAg. HBcAg had the similar results as HBx, excepthad no correlation with the expression of HSP70 (P＜0.01). These data shown thatNF-κB, cyclinD1 , Bcl-2 and HSP70 could be active and over expressed as theincreased expression level of HBx. The increased level of HBcAg could upregulatetranscription and amplification of HBV genes, which can affect the above oncogenesby increasing the copy number of HBx gene.3. The expression level of NF-κB had a positive correlation with the expression ofcyclinD1 (P＜0.01), but had no correlation with the expression of HSP70 and Bcl-2.The activation of NF-κB can increase the expression level of cyclinD1, however hadno effect on the downstream gene Bcl-2.4. There was negative correlation between the expression of HSP70 and Bcl-2(P＜0.01). There was positive correlation between the expression of HSP70 andcyclinD1(P＜0.01), but there was no correlation of the expression of cyclinD1 andBcl-2, which shows that HSP70 level has some effect on the cyclinD1 and Bcl-2.Conclusions:1. NF-κB, activated by HBx, can be transported into nucleus and bind toκB site andthen upregulate the expression of cyclinD1. The axis "High expression of HBx→Activating of NF-κB→Upregulation of cyclinD1" was thought to play an importantrole in the process of malignant transformation of liver cells and continuingproliferation of tumor cells. HBx was regarded as an promoter of HCC.2. High expression of NF-κB in cytoplasm can not make the liver cells aquiring theability of malignant transformation.3. NF-κB can promote the proliferation of tumor cells by upregulating of cyclinD1which let more G1 stage cell become S stage cell.4. NF-κB can not affect the expression of Bcl-2.5. HBV genes product and its relative pathway can affect the expression of Bcl-2which can play an important role in cirrhosis. Activation of Bcl-2 is an earlier process in the process of hepatocarcinogenesis.6. HSP70 can be an alternative molecular pathway which can regulate the apoptosisin the process of hepatocarcinogenesis.
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