【摘要】 背景与目的:已有研究表明DNA甲基化具有作为肿瘤标志的潜能。本研究旨在探讨血浆BRCA1及p16基因甲基化在乳腺癌特异诊断中的价值。方法:用甲基化特异PCR(MSP)法检测散发性乳腺癌患者癌组织及相应血浆标本中BRCA1和p16基因异常甲基化情况,同时测定CA15-3水平,并进行统计学分析。结果:乳腺癌组织中BRCA1和p16基因甲基化率分别为34.9%(22/63)和28.6%(18/63),BRCA1和p16至少一个基因(BRCA1和/或p16)甲基化率60.3%(38/63);相应血清中BRCA1和p16甲基化率依次为31.7%(20/63)和25.4%(16/63)、BRCA1和/或p16基因甲基化率为54.0%(34/63)。BRCA1和/或p16基因甲基化与肿瘤组织类型、淋巴结转移及患者居住地明显相关(P<0.01)。CA15-3单指标检测作为乳腺癌诊断的灵敏度47.6%(30/63),特异度89.7%(26/29);血浆BRCA1和/或p16甲基化检测乳腺癌的灵敏度为54.0%(34/63),特异度为93.1%(27/29)。CA15-3与BRCA1和/或p16甲基化联合检测的灵敏度可提高到84.1%,特异度也在可接受的高度93.1%(27/29)。单因素分析发现BRCA1和/或p16甲基化、组织分型和患者的居住地与乳腺癌的复发相关(P<0.05,风险指数分别为14.0、6.7和5.14),而患者绝经与否、肿瘤分级和CA15-3水平与乳腺癌复发无关(P>0.05)。多因素分析对基因甲基化、肿瘤组织分型和居住地分析提示,除患者居住地外,BRCA1和/或p16甲基化及组织分型与肿瘤的复发密切相关(P<0.05),复发风险指数分别为6.7和5.1。结论:BRCA1及p16基因甲基化检测并结合CA15-3有助于乳腺癌的特异诊断,并对乳腺癌的复发风险有预测价值。更多还原

【Abstract】 Background and Objective: Aberrant DNA methylation has the potential of being a tumor marker. This study was to evaluate the methylation statuses of BRCA1 and p16 gene promoter in tumor tissue and serum of breast cancer patients, and explore their diagnostic value. Methods: The methylation statuses of BRCA1 and p16 genes in 63 specimens of sporadic breast cancer and corresponding serum samples were detected by methylation-specific polymerase chain reaction (MSP). The serum level of CA15-3 was detected by immunofluorescent method. Results: The methylation rates of BRCA1 and p16 were 34.9% and 28.6% in tumor tissues, and were 31.7% and 25.4% in corresponding serum samples; the methylation rate of BRCA1 and / or p16 was 60.3% in tumor tissues, and was 54.0% in serum samples. The methylation rate of BRCA1 and / or p16 was related with tumor histological type, lymph node metastases and living area of patients (P<0.05). The sensitivity and specificity of CA15-3 as a diagnostic index for breast cancer were 47.6% and 93.1%; while the sensitivity and specificity of gene methylation and CA15-3 detection in combination were 84.1% and 93.1%. Univariate analysis showed that the methylation of BRCA1 and / or p16, tumor type and living area of patients were related to tumor recurrence with relative risk of 14.0, 6.7 and 5.14 (P<0.05). Multivariate analysis showed that only the methylation of BRCA1 and / or p16 and tumor type were related to tumor recurrence with relative risk of 6.7 and 5.1 (P<0.05). Conclusion: Detecting the methylation of BRCA1 and p16 gene together with CA15-3 is helpful for specific diagnosis of breast cancer, and has a predictive value for tumor recurrence.更多还原