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中国癌症防治杂志

中国癌症防治杂志 ›› 2011, Vol. 3 ›› Issue (1): 1-5.doi: doi：10.3969 / j.issn.1674-5671.2011.01.01

• 基础研究 •    下一篇

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蛋白表达的关系

陈钊宏, 黎乐群, 齐鲁楠   

  • 出版日期:2011-03-25 发布日期:2011-04-25
  • 基金资助:

    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）

Relationship between codon 249 mutation and protein expression of p53 in hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma

Chen-Zhao-Hong, LI Le-Qun, QI Lu-Nan   

  • Online:2011-03-25 Published:2011-04-25

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被引次数

23

摘要： 【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16.7%(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。

关键词: 【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

Abstract: 【Abstract】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  

Key words: 【Key words】Hepatocellular carcinoma, HBV, Aflatoxin B1, Codon 249, p53 protein