肝细胞癌组织中丙型肝炎NS_3蛋白对P53蛋白表达的影响

The effect of HCV NS 3 protein on expression of p53 gene protein in hepatocarcinogenesis

目的探讨肝细胞癌（ＨＣＣ）及其癌旁肝组织中丙型肝炎病毒（ＨＣＶ）ＮＳ３蛋白对Ｐ５３蛋白表达的影响及其在肝癌发生中的作用。方法用免疫组织化学技术检测４７例乙型肝炎病毒阴性的ＨＣＣ及其癌旁肝组织中ＨＣＶＮＳ３蛋白和Ｐ５３蛋白的表达。结果ＨＣＶＮＳ３蛋白在ＨＣＣ中的阳性率（６２％）明显低于癌旁肝组织（８３％），Ｐ＜００２５。癌组织中其表达强度与癌细胞分化程度呈相关性（Ｐ＜００２５）。Ｐ５３蛋白在癌组织中的阳性率（８１％）明显高于癌旁组织（４７％），Ｐ＜００２５；癌细胞分化愈差，表达愈强（Ｐ＜００５）；癌组织中Ｐ５３蛋白表达与ＨＣＶＮＳ３蛋白的表达无相关性（Ｐ＞０５），而癌旁肝组织中两者表达呈显著相关性（Ｐ＜００１），ＨＣＶＮＳ３蛋白阳性患者中Ｐ５３蛋白表达明显高于ＨＣＶＮＳ３阴性病例，Ｐ＜００５。结论ＨＣＶＮＳ３蛋白可能是在肝细胞转化早期通过内源性机制间接作用于Ｐ５３基因使其突变导致肝细胞癌变。

Objective To investigate hepatocarcinogenesis by detecting the effect of HCV NS 3 protein on expression of P53 protein in hepatocellular carcinoma (HCC)and pericarcinomatous liver tissue. Methods The expression of HCV NS 3 and P53 protein was detected by immuno histochemical technique (SP method)in specimens of HCC and their surrounding liver tissues from 47 patients with negative HBV. Results The positive rate of HCV NS 3 protein was lower in HCC(62%) than in pericarcinomatous liver tissue(83%) ( P <0.025).The expressive strength of HCV NS 3 protein in HCC was related to the degree of carcinomatous cell differentiation( P <0 025). The positive rate of P53 protein in carcinomatous tissue(81%) was higher than in pericarcinomatous liver tissue(47%)( P <0.025).The worse differentiaton of cancer cells, the stronger expression of P53 protein (P<0.05).The expression of P53 protein was not correlated with the expression of HCV NS 3 protein in carcinomatous tissiue ( P >0.5),whereas their expression was closely related in pericarcinomatous liver tissue( P <0.01),and the expressive rate of P53 protein in the cases of positive HCV NS 3 protein was higher than that in the cases of negative HCV NS 3 protein. Conclusion HCV NS 3 protein may exert its hepatocarcinogenic effect in early stage on host cells by endogenous pathway which may bring about mutation of p53 gene and transformation of hepatocytes.