乙肝病毒/黄曲霉毒素B_1双暴露相关性肝细胞癌的p53基因249位点突变与p53蛋白表达的关系  

Relationship between codon 249 mutation and protein expression of p53 in hepatitis B virus and aflatoxin B_1 related hepatocellular carcinoma

作　　者：陈钊宏[1] 黎乐群[2] 齐鲁楠[1] 

机构地区：[1]广西医科大学研究生学院 [2]广西医科大学附属肿瘤医院,南宁530021

出　　处：《中国癌症防治杂志》2011年第1期1-5,共5页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：国家自然科学基金资助项目(30960021);广西科学研究与技术开发计划资助项目(桂科基0731064)

摘　　要：目的研究乙肝病毒/黄曲霉毒素B1双暴露相关性肝细胞癌的p53基因249位点突变与p53蛋白表达关系。方法通过IHG特殊免疫组织化学法检测55例手术切除经病理证实为原发性肝癌的HCC组织及10例正常肝组织中AFB1-DNA加合物的暴露情况,并根据是否同时存在HBV暴露加以分组,通过免疫组化S-P法检测并比较各组间p53蛋白的表达情况。同时,通过PCR结合直接测序的方法检测其p53基因第7外显子249密码子的突变情况。结果 p53基因第7外显子249位点的突变在实验组A与对照组C中均具有较高阳性突变率,其突变率分别为68.75%(22/32)、63.64%(7/11),在对照组B中的突变率较低,为16.67%(2/12),在正常对照组中无1例出现有突变。其中实验组A与对照组B及正常对照组D的比较差异具有统计学意义(P<0.05),而与对照组C比较差异无统计学意义(P>0.05);p53蛋白在其基因249位点突变阳性组与阴性组中的表达阳性率分别为92.86%(26/28)、60.87%(16/27),差异具有统计学意义(P<0.05)。结论 HCC的发生过程中,AFB1暴露与p53第7外显子249位点的突变密切关系相关,当同时存在乙肝病毒暴露的协同作用的情况下突变率更高;p53基因的突变可能是造成HCC中p53蛋白高表达的重要因素之一。Objective To explore the mutation of p53 gene at codon 249 and the expression of p53 protein in hepatitis B virus （HBV） and aflatoxin B1 （AFB1） related hepatocellular carcinoma （HCC）. Methods AFB1-DNA adducts were detected by IHG special immunohistochemistry in 55 cases of pathologically confirmed HCC tissues and 10 cases of normal liver tissues. Polymerase chain reaction （PCR） and direct sequencing were applied to detect p53 mutations at codon 249,and immunohistochemical S-P method was applied to detect the expression of p53 protein. Results The mutation rates of codon 249 in group A （HBV＋ AFB1＋） and C （HBV-AFB1＋） were 68.75% （22/32） and 63.64% （7/11） respectively,which were higher than those in group B （HBV＋ AFB1-,16.67%,2/12） and group D （normal control,0.00%,0/10）. The expression rate of p53 in the cases with mutation at codon 249 was 92.86% （26/28）,which was higher than that without the mutation （60.87%,16/27） and the difference was statistically significant. Conclusions The mutation at codon 249 of p53 gene and AFB1 exposure are closely related during the process of HCC. The rate of codon 249 mutation is higher when the patients exposing to both HBV and AFB1. The mutation of p53 gene may be one of the important factors for causing p53 protein expression in HCC.

关 键 词：肝细胞癌 乙肝病毒 黄曲霉毒素B1 p53基因249突变 P53蛋白 

分 类 号：R735.7[医药卫生—肿瘤]