Institute for Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
Department of Clinical Genetics, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Pathol Oncol Res. 2019 Oct;25(4):1457-1465. doi: 10.1007/s12253-018-0500-y. Epub 2018 Oct 27.
Epigenetic aberrations are well known to play an important role in carcinogenesis, and also have a great potential to serve as biomarkers in many types of cancers, including ovarian cancer in which sensitive and specific biomarkers and detection methods are critically needed. The aim of this study was to investigate methylation of cadherin genes CDH10, CDH13 and CDH18 in ovarian cancer tissue by comparison with control tissue. The study group consisted of 38 patients with ovarian cancer and 25 control patients. For detection of epigenetic events we used next generation sequencing, the most important data were confirmed using high-resolution melting analysis and real-time PCR. We observed significantly higher methylation in CDH13, sporadic methylation in CDH10 and loss of methylation in CDH18 in the ovarian cancer group compared with the control group. These observations suggest that changes in methylation of cadherin genes may be one of the major mechanisms associated with ovarian cancer progression. In addition, because of the high frequency of methylation of the CDH13 gene in the early stages of ovarian cancer, the analyzed CpG sites might be good targets for next study of potential ovarian cancer screening biomarkers.
表观遗传异常在肿瘤发生中起着重要作用，也具有作为多种癌症生物标志物的巨大潜力，包括卵巢癌，其迫切需要敏感和特异性的生物标志物和检测方法。本研究旨在通过与对照组织比较，研究卵巢癌组织中钙黏蛋白基因 CDH10、CDH13 和 CDH18 的甲基化。研究组由 38 名卵巢癌患者和 25 名对照患者组成。为了检测表观遗传事件，我们使用了下一代测序，最重要的数据通过高分辨率熔解分析和实时 PCR 进行了确认。与对照组相比，我们观察到卵巢癌组中 CDH13 的甲基化明显升高，CDH10 的散发性甲基化和 CDH18 的甲基化缺失。这些观察结果表明，钙黏蛋白基因的甲基化变化可能是与卵巢癌进展相关的主要机制之一。此外，由于 CDH13 基因在卵巢癌早期甲基化频率较高，分析的 CpG 位点可能是未来研究潜在卵巢癌筛查生物标志物的良好靶点。
