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目的:探讨DNMT3a、3b蛋白表达与散发性乳腺癌BRCA1基因启动子甲基化状态及蛋白表达的相关性。方法:收集乳腺肿瘤组织及相关临床资料。采用免疫组化法检测200例散发性乳腺癌与25例乳腺纤维腺瘤组织中DNMT3a、3b蛋白的表达情况。甲基化特异性PCR检测108例散发性乳腺癌中BRCA1基因启动子甲基化状态。结果:与乳腺纤维腺瘤相比,乳腺癌组织中DNMT3a表达水平显著增高(P=0.037),DNMT3b表达水平增加不显著(P=0.478)。乳腺癌中BRCA1基因启动子存在甲基化。DNMT3a、3b过表达与乳腺癌病程晚期(TNMⅢ-Ⅳ期)显著相关(P=0.064,P=0.007);DNMT3a与BRCA1基因甲基化正相关(r=0.222,P=0.021),与BRCA1蛋白负相关(r=-0.172,P=0.022)。BRCA1蛋白表达与乳腺癌患者OS和DFS显著相关(P=0.025,P=0.027),DNMT3a表达与散发性乳腺癌OS和DFS存在一定的相关性(P=0.052,P=0.091)。结论:DNMT3a、3b高表达与乳腺癌侵袭转移、病程进展、预后相关。DNMT3a可能参与催化BRCA1基因启动子甲基化导致BRCA1蛋白表达下调的过程。抑制DNMT3a、3b蛋白可能有利于散发性乳腺癌的预防和治疗。
Objective: To investigate the relationship between DNMT3a and 3b protein methylation status and protein expression of BRCA1 promoter in sporadic breast cancer. Methods: Collect breast tumor tissue and related clinical data. The expression of DNMT3a and 3b protein in 200 cases of sporadic breast cancer and 25 cases of breast fibroadenoma were detected by immunohistochemistry. Methylation - specific PCR was used to detect the methylation status of BRCA1 promoter in 108 cases of sporadic breast cancer. Results: Compared with breast fibroadenoma, the expression of DNMT3a in breast cancer tissues was significantly increased (P = 0.037), while the expression of DNMT3b was not significantly increased (P = 0.478). BRCA1 gene promoter methylation exists in breast cancer. (P = 0.064, P = 0.007). There was a positive correlation between DNMT3a and BRCA1 gene methylation (r = 0.222, P = 0.021), which was associated with the expression of BRCA1 protein Negative correlation (r = -0.172, P = 0.022). The expression of BRCA1 protein was significantly correlated with OS and DFS in patients with breast cancer (P = 0.025, P = 0.027). DNMT3a expression was correlated with OS and DFS in sporadic breast cancer (P = 0.052, P = 0.091). Conclusion: The high expression of DNMT3a and 3b is correlated with the invasion and metastasis of breast cancer, the course of the disease and the prognosis. DNMT3a may be involved in the process of methylation of BRCA1 promoter leading to the down-regulation of BRCA1 protein expression. Inhibition of DNMT3a, 3b protein may be beneficial to the prevention and treatment of sporadic breast cancer.