Wang Xiu-Hai, Wang Pei-Lin
Department of Biology, The Qingdao University Medical College, Qingdao, Shandong, 266021, PR China.
Ai Zheng. 2003 Jul;22(7):715-8.
BACKGROUND & OBJECTIVE: The chronic infection of hepatitis B virus (HBV) is a recognized risk factor for the development of hepatocellular carcinoma (HCC); however, the precise mechanism of carcinogenesis is unknown. In order to better understand the molecular mechanism of hepatocarcinogenesis, this study was designed to investigate the relationship between the gene mutation on precore region of integrated HBV DNA, the mutation of p53 gene and the development of HCC.
The integrated HBV DNA, gene mutation on precore region of HBV DNA and p53 gene mutation were detected in 80 specimens of HCC, paratumor cirrhosis, liver cirrhosis, and normal liver tissue using polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) technique.
(1) The positive rates of integrated HBV DNA in HCC tissues, paratumor cirrhosis tissues, cirrhotic liver tissues, and normal liver tissues were 96.43%, 96.43%, 66.67%, and 6.66%, respectively. There were significant differences of the positive rates between normal liver tissues group and each of the other three groups (P< 0.005). (2) The gene mutation rates on precore region of HBV DNA in the four groups were 70.37%, 48.15%, 25.00%, and 0%, respectively. There were significant differences of the gene mutation rates among the four groups (P< 0.05). (3) The mutation rate (57.14%)of p53 gene in HCC was significantly higher than that in liver cirrhosis (16.67%) (P< 0.05). (4) The p53 gene mutation was positively associated with positivity of integrated HBV DNA and mutation on precore region of integrated HBV DNA in different liver tissues.
The HBV DNA integration and its gene mutation on precore region and p53 gene mutation probably play synergic roles in the development of HCC.
乙型肝炎病毒(HBV)慢性感染是肝细胞癌(HCC)发生的一个公认危险因素;然而,其确切的致癌机制尚不清楚。为了更好地理解肝癌发生的分子机制,本研究旨在探讨整合型HBV DNA前核心区基因突变、p53基因突变与HCC发生之间的关系。
采用聚合酶链反应(PCR)和单链构象多态性(SSCP)技术,对80例HCC标本、癌旁肝硬化组织、肝硬化组织及正常肝组织中的整合型HBV DNA、HBV DNA前核心区基因突变及p53基因突变进行检测。
(1)HCC组织、癌旁肝硬化组织、肝硬化肝组织及正常肝组织中整合型HBV DNA的阳性率分别为96.43%、96.43%、66.67%和6.66%。正常肝组织组与其他三组之间的阳性率存在显著差异(P<0.005)。(2)四组中HBV DNA前核心区的基因突变率分别为70.37%、48.15%、25.00%和0%。四组之间的基因突变率存在显著差异(P<0.05)。(3)HCC中p53基因的突变率(57.14%)显著高于肝硬化(16.67%)(P<0.05)。(4)不同肝组织中p53基因突变与整合型HBV DNA阳性及整合型HBV DNA前核心区突变呈正相关。
HBV DNA整合及其前核心区基因突变和p53基因突变可能在HCC发生中起协同作用。