BRCA1基因启动子甲基化在三阴性乳腺癌中的表达及其临床意义

摘要

Objective:To evaluate the expression of breast cancer susceptibility gene 1(BRCA1)methylation in patients with triple-negative breast cancer(TNBC)and its relationship with prognosis.Methods:A total of 524 ca-ses of breast cancer patients were collected from our hospital.The methylation status of BRCA1 promoter was observed by restriction endonuclease analysis with sodium bisulfite.The expression of BRCA1 mRNA was assessed by quantita-tive reverse transcription polymerase chain reaction(RT-PCR).The expression of BRCA1 protein was assessed by immunohistochemistry.Results:A total of 157(30.0%)patients with TNBC.There were 25(4.77%)samples with BRCA1 promoter methylation.All BRCA1 promoter methylated tumors were TNBC.In patients with TNBC,BRCA1 mRNA levels in patients with BRCA1 promoter methylation were significantly lower than those in BRCA1 promoter unmethylated patients[(0.019 ± 0.005)vs(0.095 ± 0.013),P<0.001].Immunohistochemical analysis did not detect BRCA1 protein expression in BRCA1 promoter methylation patients.The overall survival(OS)of BRCA1 pro-moter methylation was significantly lower than that of non-methylated patients(logrank P=0.038).The OS and RFS of BRCA1 protein were lower in the low expression group,but the difference was not statistically significant (logrank P=0.526,P=0.467).Conclusion:BRCA1 promoter methylation leads to a decrease in BRCA1 expression,and was associated with poor prognosis in patients with TNBC.BRCA1 promoter methylation is an important mecha-nism for the loss of BRCA1 function.%目的:评估三阴性乳腺癌(TNBC)患者中乳腺癌易感基因1(BRCA1)甲基化的表达及与患者预后的关系.方法:收集在我院甲乳科治疗的乳腺癌患者手术切除标本524例,应用联合亚硫酸氢钠限制性内切酶分析法,观察BRCA1启动子甲基化状态.应用定量逆转录聚合酶链反应评估BRCA1 mRNA表达,应用免疫组织化学法评估BRCA1蛋白表达.结果:共有157(30.0%)例TNBC患者,有25(4.77%)例存在BRCA1启动子甲基化,所有 BRCA1启动子甲基化的肿瘤均为 TNBC.TNBC患者中,BRCA1启动子甲基化患者的BRCA1 mRNA水平显著低于BRCA1启动子未甲基化患者[(0.019 ± 0.005)vs(0.095 ± 0.013),P<0.001],免疫组化分析未在BRCA1启动子甲基化患者中检测出BRCA1蛋白表达.BRCA1启动子甲基化患者的总生存率(OS)显著低于非甲基化患者(logrank P=0.038).BRCA1蛋白低表达患者的OS与RFS均低于高表达组,但差异没有统计学意义(分别logrank P=0.526,P=0.467).结论:BRCA1启动子甲基化导致了BRCA1表达的下降,并与TNBC患者较差预后相关.BRCA1启动子甲基化是一种促成 BRCA1功能丧失的重要机制.