复发转移性乳腺癌患者外周血BRCA1、CDH1、DKK1和SFRP1甲基化检测意义的研究

Detection of BRCA1,CDH1,DKK1 and SFRP1 methylation in peripheral blood cells of patients with Metastatic breast cancer

目的探讨BRCA1、CDH1、DKK1和SFRP1基因甲基化与乳腺癌患者肿瘤激素受体状态、复发转移的关系。方法利用甲基化特异性PCR法(MSP)检测115例复发转移乳腺癌患者外周血BRCA1、CDH1、DKK1和SFRP1的甲基化情况,与65例健康对照组进行比较。结果 BRCA1、CDH1和SFRP1的甲基化状态在复发转移乳腺癌患者与对照组之间存在差异。ER阳性患者外周血CDH1甲基化阳性率27.5%,ER阴性患者47.8%。ER阳性患者外周血SFRP1甲基化阳性率52.2%,ER阴性患者23.8%。有远处转移者CDH1甲基化阳性率为30.2%,而仅有局部复发转移者为63.2%。结论复发转移乳腺癌患者外周血BRCA1、CDH1和SFRP1甲基化率显著增加,CDH1和SFRP1甲基化与激素受体状态明显相关,为病情评估、治疗及愈后分析提供了一定的参考。

Objective To investigate the relationship of BRCA1,CDH1,DKK1 and SFRP1 gene methylation with ER status,relapse and metastasis in patients of Metastatic breast cancer.Methods Explore the methylation status of four genes BRCA1,CDH1,DKK1 and SFRP1 in 115 metastasis breast cancer patients＇ peripheral blood.65 patients with healthy controls with comparison.Results Percent of BRCA1.CDH1 and SFRP1methylation in patients are significantly higher compared to healthy controls.About 27.5% of patients with ER positive tumor were CDH1 methylated in peripheral blood cells,while 47.8% with ER negative tumor were methylated.In contrast,ER positive patients had a higher rate of SFRP1 methylation compared to ER negative patients.CDH1 methylation was negatively related to distant metastasis.Conclusion The four candidate genes methylation in PBC were strongly associated with clinical progress for breast cancer patients.CDH1 and SFRP1 methylation were significantly related with ER status.They provide certain reference for disease assessment,treatment and prognostic analysis.