Liu Jian, Sun Xin, Qin Sida, Wang Huangzhen, DU Ning, Li Yanbo, Pang Yamei, Wang Cuicui, Xu Chongwen, Ren Hong
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
Oncol Lett. 2016 Apr;11(4):2635-2643. doi: 10.3892/ol.2016.4274. Epub 2016 Feb 24.
The E-cadherin gene (CDH1) is associated with poor prognosis and metastasis in patients with breast cancer, and methylation of its promoter is correlated with decreased gene expression. However, there is currently no direct evidence that CDH1 promoter methylation indicates poor prognosis in patients with breast cancer. In the present study, methylation-specific polymerase chain reaction (PCR) was applied to detect the methylation status of the CDH1 promoter in 137 primary breast cancer, 85 matched normal breast tissue and 13 lung metastasis specimens. Reverse transcription-quantitative PCR was used to assess the relative expression levels of CDH1 mRNA, and correlation analysis between CDH1 methylation status, and gene expression, clinicopathological characteristics and patient survival was performed. Methylation of CDH1 was identified in 40.9% (56/137) of primary breast cancer specimens, 61.5% (8/13) of lung metastasis specimens and none of the matched normal breast specimens. The downregulation of CDH1 mRNA and E-cadherin protein expression were identified to be significantly correlated with CDH1 methylation (P<0.05). In addition, CDH1 methylation was significantly associated with lymph node metastasis and estrogen receptor status of patients (P<0.05). In univariate analyses, patients with CDH1 methylation exhibited poor overall survival (OS) and disease-free survival (DFS; P<0.05). Furthermore, multivariate analyses revealed that CDH1 methylation was an independent prognostic factor predicting poor OS (HR, 1.737; 95% CI, 0.957-3.766; P=0.041) and DFS (HR, 2.018; 95% CI, 2.057-3.845; P=0.033) in patients with breast cancer. Therefore, the present study suggests that CDH1 promoter methylation may be correlated with breast carcinogenesis and indicates poor prognosis in patients with breast cancer.
E-钙黏蛋白基因（CDH1）与乳腺癌患者的预后不良和转移相关，其启动子甲基化与基因表达降低相关。然而，目前尚无直接证据表明CDH1启动子甲基化预示着乳腺癌患者的预后不良。在本研究中，采用甲基化特异性聚合酶链反应（PCR）检测137例原发性乳腺癌、85例配对的正常乳腺组织及13例肺转移标本中CDH1启动子的甲基化状态。采用逆转录定量PCR评估CDH1 mRNA的相对表达水平，并对CDH1甲基化状态、基因表达、临床病理特征及患者生存情况进行相关性分析。在40.9%（56/137）的原发性乳腺癌标本、61.5%（8/13）的肺转移标本中检测到CDH1甲基化，而配对的正常乳腺标本中均未检测到。CDH1 mRNA下调及E-钙黏蛋白蛋白表达降低与CDH1甲基化显著相关（P<0.05）。此外，CDH1甲基化与患者的淋巴结转移及雌激素受体状态显著相关（P<0.05）。单因素分析显示，CDH1甲基化患者的总生存期（OS）和无病生存期（DFS）较差（P<0.05）。此外，多因素分析显示，CDH1甲基化是预测乳腺癌患者OS不良（HR，1.737；95%CI，0.957 - 3.766；P=0.041）和DFS不良（HR，2.018；95%CI，2.057 - 3.845；P=0.033）的独立预后因素。因此，本研究提示CDH1启动子甲基化可能与乳腺癌发生相关，并预示乳腺癌患者预后不良。
