羧基端截短乙肝病毒x蛋白和加帽蛋白B在肝癌组织中的表达及临床意义

Expression of carboxy-terminal truncated hepatitis B virus x protein and capping protein B in hepatocellular carcinoma tissues and its clinical significance

目的:探讨羧基端截短的乙肝病毒x蛋白(Ct-HBx)和加帽蛋白B(CAPZB)在肝癌组织中的表达及临床意义。方法:应用PCR及测序技术检测41例HBsAg(+)的肝癌及癌周组织中HBx基因整合状态;采用免疫组化技术分别检测表达全长HBx和Ct-HBx的肝癌及癌周组织中CAPZB表达水平,分析CtHBx与CAPZB表达的关系,以及与临床病理特征之间的相关性。结果:(1)全长HBx基因在肝癌组织及癌周组织中表达率分别为20.6%(7/34)和40%(12/30),两者比较,差异无统计学意义(P=0.090);而3’末端缺失HBx基因在肝癌组织及癌周组织中表达率分别为79.4%(27/34)和53.3%(16/30),两者比较,差异有统计学意义(P=0.027)。(2)羧基端截短≥14个氨基酸(即碱基缺失≥42 bp)的标本有13例。对比全长HBx阳性的肝癌组织,CAPZB在Ct-HBx阳性肝癌组织中的表达明显减低;CAPZB在Ct-HBx阳性的肝癌及癌周组织中阳性表达率分别为23.1%(3/13)和84.6%(11/13),两者比较,差异有统计学意义(P=0.005)。CAPZB在肝癌组织中的表达水平与肝癌转移呈负相关关系(P=0.017)。结论:CAPZB在肝癌组织中的表达下调与HBx蛋白羧基端缺失突变有关,且与肝内转移发生相关,提示CAPZB可能参与了Ct-HBx介导的肝癌进展机制。

Objective：To investigate the expression of carboxy-terminal truncated hepatitis B virus x protein （Ct-HBx） and capping protein B （CAPZB） in hepatocellular carcinoma tissues and its clinical significance. Methods：The HBx gene integration status in 41 HBsAg （＋） hepatocellular carcinoma and para-carcinoma tissues was determined by PCR and sequencing technology. The expression level of CAPZB in the full-length HBx and Ct-HBx hepatocellular carcinoma and para-carcinoma tissues was examined by immunohistochemical technology, respectively. The relationship between Ct-HBx and CAPZB expression was analyzed, and their correlation between clinicopathological features was analyzed. Results ： （ 1 ） The expression rate of full-length HBx gene in hepatocellular carcinoma and para-carcinoma tissues was 20. 6% （7/34） and 40% （12/30）, respectively, and there was no statistically significant difference between them （P = 0.090）. The expression rate of 3＇ terminal truncated HBx gene was 79.4% （27/34） and 53.3% （16/30） in hepatocellular carcinoma and para- carcinoma tissues ,respectively, and the difference was statistically significant （P = 0.027）. （2） There were 13 specimens with truncated carboxy-terminal ≥ 14 amino acids （ base deletion ≥ 42 bp）. Compared with full- length HBx-positive hepatocellular carcinoma tissues, the expression of CAPZB in Ct-HBx-positive carcinoma tissues was significantly decreased. The positive expression rates of CAPZB in Ct-HBx-positive hepatocellular carcinoma and para-carcinoma tissues were 23.1% （3/15） and 84.6% （ 11/13）, respectively, and there was statistically significant difference between them （P = 0.005）. The expression level of CAPZB in hepatocellular carcinoma tissues was negatively correlated with the metastasis of hepatocellular carcinoma （ P = 0. 017 ）. Conclusion：RThe down-regulation of CAPZB expression in hepatocellular carcinoma tissues is related to the mutation of Ct-HBx and the occurrence of intrahepatic metastasis, suggesting that CAPZB may be involved in the mechanism of Ct-HBx-mediated hepatocellular carcinoma progress.