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Evaluation of methylation modification in E-cadherin gene and its application in the improvement of breast cancer

机译:E-钙粘蛋白基因甲基化修饰的评价及其在乳腺癌改良中的应用

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CDH1 (E-cadherin), which mediates cell-cell interaction and polarity, is known as glycoprotein in cytoskeleton. The objective of this study was to evaluate CDH1 expression loss as the metastatic marker by defining the methylation pattern in the promoter region and determining whether or not the methylation pattern changes in correlation with a kind of tumor, grade and metastatic status. Fifty patients with breast carcinoma were enrolled in this study and fifty normal breast tissues were obtained from an adjacent tumor area as control from the same patients’ breast. All of these patients had different grades, metastasis status and tumor kind. Fresh tissue sections of breast cancers were obtained and their DNA was isolated, bisulfite treated, PCR amplified and analyzed for sequencing.?The loss of CDH1 was assessed as percentage of methylation (full, partial and non-methylated) in the promoter region, and the number of CpG sites involved in methylation was assessed as the methylation pattern. The percentage of CDH1 gene promoter methylation in the tumor samples was 44% for full methylation, 50% for partial methylation and 6% for non-methylated. There was significant difference between normal and tumor tissues in methylated CpG sites and also between different grades and kinds of tumor. More so, there was no significant variation in the recurrence state of tumor. Even though?loss of CDH1 expression in breast cancer has been established before, its critical role in cell-cell contact can reflect the metastatic effect of the lost expression during the metastatic phase of cancer. However, methylation pattern significantly differs in high grade tumor samples (p<0.00).
机译:CDH1(E-钙粘着蛋白)介导细胞间相互作用和极性,在细胞骨架中被称为糖蛋白。这项研究的目的是通过定义启动子区域的甲基化模式并确定甲基化模式是否与某种肿瘤,级别和转移状态相关联来评估作为转移标记的CDH1表达损失。这项研究招募了50名乳腺癌患者,并从同一患者的乳房中从相邻的肿瘤区域获得了50例正常乳腺组织作为对照。所有这些患者均具有不同的等级,转移状态和肿瘤种类。获得了乳腺癌的新鲜组织切片,并分离了它们的DNA,进行了亚硫酸氢盐处理,PCR扩增并进行了测序分析。甲基化涉及的CpG位点的数量被评估为甲基化模式。肿瘤样品中CDH1基因启动子甲基化的百分比为:全甲基化为44%,部分甲基化为50%,非甲基化为6%。甲基化CpG位点的正常组织和肿瘤组织之间以及不同级别和种类的肿瘤之间都存在显着差异。更重要的是,肿瘤的复发状态没有显着变化。尽管CDH1在乳腺癌中的表达已经确立,但它在细胞间接触中的关键作用可以反映出癌症转移阶段丢失的表达的转移作用。然而,甲基化模式在高等级肿瘤样品中显着不同(p <0.00)。

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