整合型HBVDNA前C区突变和p53基因突变与肝细胞癌发生的关系

背景与目的:乙型肝炎病毒 (hepatitis B virus, HBV)的慢性感染是肝细胞癌 (hepatocellular carcinoma, HCC)发生的主要危险因素,但其确切的作用机理还不清楚.本研究拟探讨整合型 HBV 前 C区突变、 p53基因突变与 HCC发生的关系,以期更好地了解 HCC发生的分子机理.方法 :应用聚合酶链反应技术( PCR)和聚合酶链反应-单链构象多态 (single strand conformation polymorphism analysis of polymerase chain reaction products, PCR SSCP) 技术对 28例肝癌组织、 25例癌旁肝硬化组织、 12例肝硬化组织和 15例正常肝组织标本内的整合型 HBV DNA及其前 C区基因突变和肝细胞 p53基因突变进行检测分析.结果:( 1)正常肝组织、肝硬化组织、癌旁肝硬变组织和肝癌组织中整合 HBV DNA 阳性率分别为 6.66%、 66.67%、 96.43% 和 96.43%,正常肝组织与其它三组间阳性率差异有非常显著性( P< 0.005); (2)4组整合型 HBV DNA前 C区突变率分别为 0%、 25.00% 、 48.15% 和 70.37%, 4组间的突变率差异有显著性( P< 0.05); ( 3)肝癌组织的 p53基因突变率( 57.14%)明显高于肝硬化组( 16.67%) (P< 0.05);( 4)不同肝组织中 p53基因突变率与整合 HBV DNA 阳性率、 HBV前 C区基因突变率呈正相关.结论:在肝细胞癌的发生、发展中整合 HBV DNA及其前 C区基因突变和 p53基因突变可能起协同作用.

Relationship between mutation on precore region of integrated HBV DNA and p53 gene mutation in hepatocellular carcinoma

BACKGROUND &OBJECTIVE:The chronic infection of hepatitis B virus (HBV)is a recog nized risk factor for the de velopment of hepatocellular carcinoma (HCC);however,the precise mechanism of c arcinog enesis is unknown.In order to better understa nd the molecular mechanism of hepatocarcinog enesis,this study was desig ned to investig a te the relationship between the g ene mutation on precore reg ion of integ rated HBV DNA,the mutation of p53g ene and the developm ent of HCC.METHODS :The integ rated HBV DNA,g ene mutation on precore reg ion of HBV DNA and p53g ene mutation were detected in 80specimens of HCC,paratumor cirrhosis,liver cirrhos is ,and normal liver tissue using polymeras e chain reaction(PCR)and sing le strand conformation polymorphism(SSCP)technique.RESULTS :(1)The positive rates of integ rated HBV DNA in HCC tis sues ,paratumor cirrhosis tissues ,cirrhotic liver tissues,and normal liver tissues were 96.43%,96.43%,66.67%,and 6.66%,respectively.Th ere were sig nificant differences of the positive rates between normal liver tissues g roup and each of the other th ree g roups (P<0.005).(2)The g ene mutation rates on precore re g ion of HBV DNA in the four g roups were 70.37%,48.15%,25.00%,and 0%,respectively.There were sig nificant differences of the g ene mutation r ates among the four g roups (P<0.05).(3)The mutation rate(57.14%)of p53g ene in HCC was sig nificantly hig her than th at in liver cirrhosis(16.67%)(P<0.05).(4)The p53g ene mutation was positively associated with positivity of integ rated HBV DNA and mutation on precore reg io n of integ rated HBV DNA in different l iver tissues.CONCLUSION:The HBV DNA integ ration and its g ene m utation on precore reg ion and p53g ene mutation probably play synerg ic roles in the development of HCC.