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

Abstract

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).