【摘要】 背景与目的:在乳腺癌发生、发展过程中,甲基化异常是导致抑癌基因失活的重要机制,是一种可用于肿瘤诊断及预后判断、有价值的生物标志物。本研究旨在通过检测乳腺癌组织及其相应的血浆循环DNA中Sox17基因的甲基化状况,探讨其在乳腺癌早期诊断和预后判断方面的应用价值。方法:采用甲基化特异性聚合酶链反应(methylation specific-PCR,MSP)法,对86例乳腺癌组织、36例乳腺良性肿瘤的癌旁正常组织及其配对的血浆循环DNA中Sox17基因启动子甲基化进行检测,并结合乳腺癌的主要临床病理特性进行分析。结果:86例乳腺癌组织中Sox17基因启动子的甲基化率为77.9%(67/86),与其相应血浆循环DNA中Sox17基因启动子的甲基化率为61.6%(53/86),36例癌旁正常乳腺组织及血浆中均未检测到Sox17基因异常甲基化。患者血浆循环DNA中Sox17基因启动子的甲基化与肿瘤组织中该基因的甲基化显著相关(r=0.502,P=0.000)。在乳腺癌组织标本中Sox17基因甲基化率与患者肿瘤分期(χ2=6.18,P=0.041)、淋巴结转移(χ2=13.54,P=0.001)显著相关,在血浆标本中,Sox17基因甲基化率与患者肿瘤分期(χ2=27.06,P=0.000)、肿瘤大小(χ2=9.65,P=0.007)及淋巴结转移(χ2=20.80,P=0.000)显著相关,与患者年龄、组织学分级及ER、PR、HER-2/neu等指标差异无统计学意义(P>0.05)。结论:Sox17基因启动子甲基化在乳腺癌的发生、发展中起着重要作用,可能与乳腺癌的预后相关。血浆中Sox17基因甲基化,是一个有潜在应用价值的生物标志物。更多还原

【Abstract】 Background and purpose: Aberrant DNA methylation that leads to the inactivation of tumor suppressor genes plays important roles in development and progression of breast cancer. Clinically, related gene methylation is considered to be a promising biomarker for tumor diagnosis and prognosis. This study aimed to investigate the methylation status of Sox17 gene in breast cancer tissue and its corresponding plasma circulating DNA, as well as to investigate its value in breast cancer early diagnosis and prognosis. Methods: The Sox17 gene promoter methylation status was detected by MSP in 86 cases of breast cancer, 36 normal breast tissues and its paired plasma DNA, the results were analyzed with corresponding clinical and pathological features. Results: The frequency of Sox17 gene methylation rate among 86 breast cancer tissues was 77.9%(67/86), and was 61.6%(53/86)in plasma circulating DNA, however, no Sox17 gene methylation was found in normal breast tissues. Sox17 gene promoter methylation in plasma circulating DNA was significantly associated with the methylation status in tumor tissues(r=0.502, P=0.000). In breast cancer tissue specimens, Sox17 methylation status was significantly correlated with tumor stage(χ2=6.18, P=0.041) and lymph node metastasis(χ2=13.54, P=0.001); Sox17 gene methylation rate was significantly correlated with tumor stage(χ2=27.06, P=0.000), tumor size(χ2=9.65, P=0.007) and lymph node metastasis(χ2=20.80, P=0.000) in plasma samples, and there was no significant difference of Sox17 gene methylation between patient age, histological grade and ER, PR, HER-2/neu status. Conclusion: Sox17 gene promoter methylation plays an important role in the carcinogenesis and development of breast cancer, and may be associated with the prognosis of breast cancer. Furthermore, methylated Sox17 gene may be a useful tumor biomarker in plasma circulating DNA for breast cancer detection and disease monitoring.更多还原