Naghitorabi Mojgan, Mohammadi-Asl Javad, Sadeghi Hamid Mir Mohammad, Rabbani Mohammad, Jafarian-Dehkordi Abbas, Javanmard Shaghayegh Haghjooy
Department of Pharmaceutical Biotechnology, Isfahan University of Medical Sciences, Isfahan, Iran.
Cancer, Petroleum and Environmental Pollutants Research Centre, Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran.
Adv Biomed Res. 2016 May 30;5:91. doi: 10.4103/2277-9175.183139. eCollection 2016.
E-cadherin (CDH1) plays an important role in cell-cell adhesion of epithelial tissues. Loss of E-cadherin expression can lead to loss of tissue integrity, metastasis, and cancer progression. Also loss of E-cadherin expression might be related to aberrant promoter methylation of the CDH1 gene. Many studies have been performed on CDH1 promoter methylation, especially in breast cancer. Although most of the studies have used qualitative methods for methylation analysis, this study is designed to quantitatively investigate CDH1 promoter methylation in breast cancer and its correlation with patients' clinicopathological features.
Using differential high resolution melting analysis (D-HRMA), the methylation level of the CDH1 gene promoter was quantified in 98 breast cancer formalin-fixed paraffin-embedded (FFPE) tissues and also 10 fresh frozen normal breast tissues.
All samples were detected to be methylated at the CDH1 promoter region. About 74.5% of the breast cancer samples were hypermethylated with an average methylation level of around 60%, while 25.5% of the patients were methylated with the mean methylation level of about 33%, and 90% of the normal samples had a mean methylation level of about 18%. Statistical analyses represented a significant correlation between CDH1 promoter methylation and cancer progression hallmarks, such as, clinical stage, nodal involvement, tumor size, and histological grade.
In summary, quantitation of CDH1 promoter methylation can serve as a diagnostic and prognostic tool in breast cancer. Also D-HRMA can be used as a fast and reliable method for quantitation of promoter methylation.
E-钙黏蛋白（CDH1）在上皮组织的细胞间黏附中起重要作用。E-钙黏蛋白表达缺失可导致组织完整性丧失、转移及癌症进展。此外，E-钙黏蛋白表达缺失可能与CDH1基因启动子异常甲基化有关。许多关于CDH1启动子甲基化的研究已经开展，尤其是在乳腺癌方面。尽管大多数研究采用定性方法进行甲基化分析，但本研究旨在定量研究乳腺癌中CDH1启动子甲基化及其与患者临床病理特征的相关性。
采用差异高分辨率熔解分析（D-HRMA）对98例乳腺癌福尔马林固定石蜡包埋（FFPE）组织及10例新鲜冷冻正常乳腺组织中CDH1基因启动子的甲基化水平进行定量分析。
所有样本在CDH1启动子区域均检测到甲基化。约74.5%的乳腺癌样本高度甲基化，平均甲基化水平约为60%，而25.5%的患者甲基化，平均甲基化水平约为33%，90%的正常样本平均甲基化水平约为18%。统计分析表明CDH1启动子甲基化与癌症进展特征，如临床分期、淋巴结受累、肿瘤大小和组织学分级之间存在显著相关性。
总之，CDH1启动子甲基化定量可作为乳腺癌的诊断和预后工具。此外，D-HRMA可作为一种快速可靠的启动子甲基化定量方法。
