Expression Of Nf-κB,Bcl-2,fas/fasl And Their Role In Pathogenesis And Development Of Hepatocellular Carcinoma(HCC)

ObjectiveTo explore the mechanisms of NF-κB,Bcl-2 and Fas/FasL in hepatocellular carcinoma (HCC) of AFP(+) group and AFP (-) group and benign liver group by investigating their protein expression in combination with clinical and pathological characteristics.MethodsImmunohistochemical technique was used to detect protein expression proportion and the level of NF-κB,Bcl-2 and Fas/FasL in 20 HCC specimens of AFP (+) group, 20 specimens of AFP (-) group and 10 specimens of benign liver group. the experimental data were analyzed using semi-quantitative count and SPSS13.0.ResultsExpression of NF-κB in human HCC of AFP (+), AFP (-) and benign liver tissues was 75.00% (15/20),40.00% (8/20) and 0% (0/10), respectively. Expression of NF-κB in AFP(+) group was significantly higher than that of AFP(-) group and benign liver group (P<0.05), and was significantly correlated with that of AFP, HBsAg, portal vein invasion, pathological grade, tumor size (P<0.05).no correlation was found in expression of NF-κB with age, tumor invasion and metastasis (P>0.05).The expression of Bcl-2 protein in human HCC of AFP(+),AFP(-),and benign liver tissues was 55.00% (11/20), 35.00% (7/20) and 0% (0/10),respectively. the expression of AFP (+) group was higher than that of AFP(-) group without statistical significane (P>0.05). The expression of Bcl-2 was significantly correlated with HBsAg, pathological grade, and tumor size (P<0.05), but no statistically significance was found with age, AFP, portal vein invasion, tumor invasion and metastasis (P>0.05).The expression of Fas and FasL protein in human HCC of AFP (+), AFP (-) and benign liver tissues was 75.00% (15/20) and 60.00% (12/20), 75.00% (15/20) and 80.00%(16/20), 30.00% (3/10) and 30.00% (3/10). no statistical significance was found between AFP (+) group and AFP (-) group (P>0.05). no statistically significant correlation was found with age, AFP, HBsAg, portal vein invasion, pathological grade, and tumor size (P>0.05), but statistical significance was found in correlation with tumor invasion and metastasis (P<0.05). In 13 HCC specimens with invasion and metastasis, expression of Fas and FasL protein was 100% (13/13).The expression of NF-κB,Bcl-2,Fas and FasL protein in all 40 HCC specimens was 57.50%(23/40), 45.00%(18/40), 75.00%(30/40)and 70% (28/40),which was both significantly higher than that of benign liver tissues (P<0.05).NF-κB expression in HCC was positively correlated with Bcl-2 expression(r=0.778,P<0.01),which was positively correlated with Fas expression(r=0.39, P<0.05)and negatively associated with FasL expression(r=-0.285,P>0.05). We also found 19 cases of HBsAg (+) patient in 20 cases of AFP (+) group. 6 AFP (-) cases were out of 7 HBsAg (-) cases. The serumα-fetal protein (AFP) level was significantly correlated with that of HBsAg (r=0.329,P<0.05).Conclusions1. The expression of NF-κB protein were significantly correlated with that of AFP, HBsAg, portal vein invasion, pathological grade and tumor size in HCC, which was suggestive of its involvement in the development of HCC. NF-κB protein may be used as an indicator for the grade of malignancy in HCC patients.2. The expression of NF-κB protein in AFP(+) group was significantly higher than that in AFP (-) group. serum a-fetal protein (AFP) level was also found significantly correlated with that of HBsAg. Therefore, HCC tissue with HBsAg(+) may have elevated AFP by activating the NF-κB signaling pathway.3. Expression of Bcl-2 protein in HCC was significantly correlated with that of HBsAg, pathological grade, and tumor size (P<0.05), but no statistical significant correlation was found with age, AFP, portal vein invasion, tumor invasion and metastasis (P>0.05). However, the expression of NF-κB protein was positively correlated with that of Bcl-2 protein expression in HCC, which suggested that HCC tissue may activate NF-κB signaling pathway via increasing its downstream regulation of antiapoptotic protein Bcl-2 and inhibit apoptosis in hepatoma cells. However, up-regulation of Bcl-2 is one of the links in the development of HCC.4. The expression of Bcl-2 was positively correlated with that of Fas, which suggested that Bcl-2 could induce desensitization of HCC to Fas-mediated apoptosis, which could consequently evade attacks of the immune system.5. Expression of Fas and FasL protein could be an indicator for invasion and metastasis due to the positive rate of 100% (13/13) in HCC.6. The up-regulation and correlation of NF-κB,Bcl-2,Fas and FasL protein in HCC suggested multifactorial pathways for pathogenesis and development of HCC.