散发性乳腺癌细胞14-3-3σ异常甲基化及其蛋白表达的关系  

14-3-3σ Hypermethylation and Its Relationship with Protein Expression in Sporadic Breast Carcinogenesis

作　　者：王玉平[1] 冯景[1] 吕军[1] 谢飞[1] 郭毅飞[1] 张吉才[1] 

机构地区：[1]郧阳医学院附属太和医院检验科,湖北十堰442000

出　　处：《湖北医药学院学报》2009年第5期437-440,412,共5页Journal of Hubei University of Medicine

基　　金：湖北省自然基金项目(No.2007ABA371);湖北省教育厅中青年人才项目(No.Q20082407);湖北省杰出青年人才项目(No.2008154)

摘　　要：目的:探讨散发性乳腺癌癌变过程14-3-3σ基因启动子异常甲基化状况及其与转录表达的关系。方法:用甲基化特异PCR方法对散发性乳腺癌病人癌组织及正常组织进行14-3-3σ异常甲基化检测;用免疫组织化学测定14-3-3σ蛋白表达。结果:68例散发性乳腺癌组织中,14-3-3σ基因启动子异常甲基化率为90%(61/68),部分不典型增生病例检出异常甲基化18%(2/13),而正常组织未检出。14-3-3σ基因启动子异常甲基化与患者居住地、组织分型、分级和淋巴结转移相关(P<0.05)而与年龄无相关性(P>0.05),14-3-3σ基因甲基化与其蛋白表达下降呈良好的一致性(P<0.05)。单变量分析发现,淋巴结转移与预后明显相关(风险指数为:5.0,P=0.02)。14-3-3σ基因甲基化与否并不影响乳腺癌的五年生存率(P>0.05)。结论:14-3-3σ基因异常甲基化参与乳腺癌癌变过程,是其蛋白表达下降的重要原因之一,但不影响乳腺癌的生存率。Objective To explore the relationship between 14-3-3σ gene promoter region hypermethylation and its transcription in sporadic breast carcinogenesis.Methods Hypermethylation of 14-3-3σ gene was detected by sensitive MSP assay in carcinous and normal tissue,and its protein expression was detected with SP immuno histochemistry assay.Results The hypermethylation frequencies of 14-3-3σ were 90%(61/68) in patients with sporadic breast cancer.Hypermethylation was detected in portions(2/18) of hyperplastic samples,and no hypermethylation was detected in normal tissue.The hypermethylation change of 14-3-3σ gene was markedly related with residential district,histological type,grade and lymph node metastases(P <0.05),but had no correlation with age(P >0.05),there was a closely consistent between 14-3-3σ methylation and the decrease of protein expression(P <0.05).Univariate analysis showed that the lymph node metastases were correlated with tumor recurrence relative risk of 5.0,P =0.02,wether the 14-3-3σ methylation had no effect on the five-year survival rate.Conclusion 14-3-3σ methylation may involve in the development of breast carcinogenesis,which should be an important factor of the decreased expression,but may have no effect on the survival rate.

关 键 词：散发性乳腺癌 癌变过程 DNA甲基化 14-3-3Σ基因 

分 类 号：R737.9[医药卫生—肿瘤]