多基因甲基化对散发性乳腺癌的诊断价值  

Diagnostic Value of Multigenes Methylation in Patients with Sporadic Breast Cancer

作　　者：王玉平[1] 吕军[2] 陈咏梅[2] 汤显斌[2] 谢飞[2] 张吉才[2] 冯景[3] 

机构地区：[1]湖北医药学院附属太和医院消毒供应室,湖北十堰442000 [2]湖北医药学院附属太和医院检验科,湖北十堰442000 [3]南方医科大学附属奉贤医院检验科,上海201400

出　　处：《郧阳医学院学报》2010年第6期491-499,499,共6页Journal of Yunyang Medical College

基　　金：湖北省杰出青年人才项目(2008154);湖北省自然基金项目(2007ABA371);湖北省教育厅中青年人才项目(Q20082407);湖北医药学院中青年创新团队项目(CXX200805)

摘　　要：目的:探讨血清表观遗传学改变即DNA甲基化对散发性乳腺肿瘤的诊断价值。方法:用甲基化特异PCR检测了102例散发性乳腺癌患者及20例健康对照者血清BRCA1,p16和14-3-3 sigma基因甲基化状况。结果:102例散发性乳腺癌患者血清中p16基因甲基化率为29%,BRCA1为32%,14-3-3 sigma为82%,与肿瘤分级和ER受体表达明显相关。p16基因甲基化与组织分型有关,p16与BRCA1基因甲基化和PR相关,14-3-3 sigma基因甲基化与淋巴结转移有关。70%p16、75.8%BRCA1甲基化患者显示血清CEA水平升高,69.7%显示CA153水平升高。多因素分析发现,血清BRCA1和/或p16甲基化可以预示预后不良,死亡风险指数达6.0。结论:散发性乳腺癌患者BRCA1/p16基因甲基化作为肿瘤标志物明显优于蛋白类(CEA、CA153)标志物。Objective To investigate the diagnostic value of epigenetics change,definitely aberrant DNA methylation in patients with sporadic breast cancer.MethodsThe status of BRCA1,p16 and 14-3-3 sigma methylation in serum of 102 patients with sporadic breast cancer were examined by methylation-specific PCR assay,and another20 serum samples from healthy volunteers were also examined as control group.ResultsThe panel genes methylation frequency of p16,BRCA1 and 14-3-3 sigma in 102 sporadic breast cancers were 29%,32%,82%,respectively,which were significantly associated with pathological grades and estrogen receptor status.And only p16 methylation was associated with histologic type.p16 and BRCA1 methylation were associated with progesterone receptor status,and 14-3-3 sigma was significantly associated with lymph node metastases.70% patients with p16 hypermethylation showed elevating serum CEA levels.The 75.8% of sporaidc breast cancer patients with BRCA1 hypermethylation showed elevating serum CEA levels,while 69.7% showed elevated serum CA153 levels.Multivariate analysis showed methylated BRCA1 and/or p16 serum DNA to be independently associated with poor outcome,with a relative risk for death of 6.0.ConclusionBRCA1/p16 methylation as marker in serum of patients with sporadic breast cancer may be more powerful than protein prognostic biomarker.

关 键 词：基因甲基化 散发性乳腺癌 肿瘤标志物 

分 类 号：R737.9[医药卫生—肿瘤]