DNA Methyltransferase 1/3a Overexpression in Sporadic Breast Cancer is Associated with Reduced Expression of Estrogen Receptor-Alpha/Breast Cancer Susceptibility Gene 1 and Poor Prognosis
DNA Methyltransferase 1/3a Overexpression in Sporadic Breast Cancer is Associated with Reduced Expression of Estrogen Receptor-Alpha/Breast Cancer Susceptibility Gene 1 and Poor Prognosis
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DOI：
10.1002/mc.22133
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发表时间：
2015-09-01
影响因子：
4.6
通讯作者：
Wei, Minjie
中科院分区：
文献类型：
--
作者：
Yu, Zhaojin;Xiao, Qinghuan;Wei, Minjie
DNA甲基转移酶（DNMT），包括DNMT1、3a和3b，在许多恶性肿瘤的进展中发挥重要作用。然而，目前尚不清楚 DNMT 的表达是否与乳腺癌的发生有关。本研究旨在探讨DNMT蛋白在散发性乳腺癌中的临床意义。我们使用免疫组织化学方法研究了 256 例乳腺癌和 36 例乳腺纤维腺瘤中 DNMT1、3a 和 3b 的表达。 DNMT1和3a在乳腺癌中的表达显着高于纤维腺瘤。在乳腺癌中，DNMT1的表达与淋巴结转移显着相关（P=0.020），DNMT3a和3b的表达与晚期临床分期显着相关（分别P=0.046和0.012）。 DNMT1/3a 的过表达与启动子高甲基化以及 ER 和 BRCA1 表达减少相关。 DNMT1 或 DNMT3a 的表达水平与乳腺癌患者亚组（年龄 50 岁、ER 阴性状态或 HER2 阳性状态的患者）的 DFS 或 OS 显着缩短相关。 DNMT1的表达或DNMT1和3a的联合表达与接受化疗和内分泌治疗的患者的不良预后相关，但与单独接受化疗的患者无关。这些发现表明DNMT1和3a可能参与散发性乳腺癌的进展和预后。 (C) 2014 年 Wiley 期刊公司。
DNA methyltransferases (DNMTs), including DNMT1, 3a, and 3b, play an important role in the progression of many malignant tumors. However, it remains unclear whether expression of DNMTs is associated with the development of breast cancer. This study aimed to explore the clinical significance of DNMT proteins in sporadic breast cancer. We investigated the expression of DNMT1, 3a, and 3b in 256 breast cancer and 36 breast fibroadenoma, using immunohistochemistry. The expression of DNMT1 and 3a was significantly higher in breast cancer than in fibroadenoma. In breast cancer, the expression of DNMT1 was significantly correlated with lymph node metastasis (P=0.020), and the expression of DNMT3a and 3b was significantly correlated with advanced clinical stages (P=0.046 and 0.012, respectively). Overexpression of DNMT1/3a was correlated with promoter hypermethylation and reduced expression of ER and BRCA1. The expression levels of DNMT1 or DNMT3a were associated with a significantly shorter DFS or OS in a subgroup of breast cancer patients (patients with the age 50 years old, ER-negative status, or HER2-postive status). The expression of DNMT1 or a combined expression of DNMT1 and 3a was associated with poor prognosis in patients who received chemotherapy and endocrine therapy, but not in patients who received chemotherapy alone. These findings suggest that DNMT1 and 3a may be involved in the progression and prognosis of sporadic breast cancer. (C) 2014 Wiley Periodicals, Inc.