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目的探讨外周血浆中游离DNA变异在乳腺癌早期诊断、疗效评估和复发监控中应用的可行性。方法采用甲基化特异性PCR(MSP)方法,检测84例乳腺癌患者肿瘤组织、癌旁正常腺体组织及外周血浆中游离的肿瘤相关DNA钙黏素E(E-cadherin)和APC基因启动子甲基化畸变状况,选择10例乳腺良性疾病患者的血浆作为正常对照。结果乳腺癌肿瘤组织E-cadherin和APC基因启动子甲基化畸变频率分别为52.4%和45.2%,相应外周血浆中相同的DNA变异阳性检出率分别为33.3%和31.0%。外周血浆中DNA甲基化变异与肿瘤组织的甲基化畸变状况显著相关(E- cadherin,P<0.001;APC,P=0.002)。血浆DNA E-cadherin和APC基因甲基化畸变检测的灵敏度分别为63.6%和63.2%,特异度分别为100%和95.7%。肿瘤组织及外周血浆中游离DNA甲基化畸变与临床分期、病理类型、肿块大小及受体状况无相关性(P>0.05)。癌旁正常腺体组织及健康对照血浆中均未检测到E-cadherin和APC基因甲基化变异。结论在受检乳腺癌患者中,约1/3外周血浆中可检测到与原发肿瘤相同的E-cadherin和(或)APC基因甲基化畸变,与临床分期无相关性。在乳腺癌早期诊断、疗效评估和复发监控中,检测外周血浆中游离的肿瘤相关DNA变异有一定的可行性。
Objective To investigate the feasibility of the application of free DNA variation in peripheral plasma in the early diagnosis, curative effect evaluation and recurrence monitoring of breast cancer. Methods The methylation-specific PCR (MSP) method was used to detect the tumor-associated DNA-E and cadherin (APC) genes in tumor tissues, adjacent normal gland tissues and peripheral plasma in 84 patients with breast cancer. Sub-methylation aberration, the selection of 10 cases of benign breast disease in patients with plasma as a normal control. Results The methylation frequencies of E-cadherin and APC in breast cancer were 52.4% and 45.2%, respectively. The positive rates of DNA mutation in the corresponding peripheral plasma were 33.3% and 31.0%, respectively. DNA methylation variation in peripheral plasma was significantly associated with aberrant methylation of tumor tissue (E-cadherin, P <0.001; APC, P = 0.002). The sensitivity of detection of methylation of plasma E-cadherin and APC genes were 63.6% and 63.2% respectively, and the specificity was 100% and 95.7% respectively. Tumor tissue and peripheral plasma free DNA methylation aberrations and clinical stage, pathological type, tumor size and receptor status no correlation (P> 0.05). There was no methylation mutation of E-cadherin and APC gene in adjacent normal gland tissues and healthy controls. Conclusions The methylation aberration of E-cadherin and / or APC gene in about one-third of peripheral blood plasma was detected in the breast cancer patients, which was the same as the primary tumor, and had no correlation with clinical stage. In the early diagnosis of breast cancer, efficacy evaluation and recurrence monitoring, detection of peripheral plasma free tumor-associated DNA variation has a certain feasibility.