Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong; Department of Surgery, The Chinese University of Hong Kong, Hong Kong.
Semin Cancer Biol. 2019 Apr;55:90-105. doi: 10.1016/j.semcancer.2018.04.002. Epub 2018 Apr 14.
Altered epigenetic regulation is central to many human diseases, including cancer. Over the past two decade, major advances have been made in our understanding of the role of epigenetic alterations in carcinogenesis, particularly for DNA methylation, histone modifications and non-coding RNAs. Aberrant hypermethylation of DNA at CpG islands is a well-established phenomenon that mediates transcriptional silencing of tumor suppressor genes, and it is an early event integral to gastrointestinal cancer development. As such, detection of aberrant DNA methylation is being developed as biomarkers for prognostic and diagnostic purposes in gastrointestinal cancers. Diverse tissue types are suitable for the analyses of methylated DNA, such as tumor tissues, blood, plasma, and stool, and some of these markers are already utilized in the clinical setting. Recent advances in the genome-wide epigenomic approaches are enabling the comprehensive mapping of the cancer methylome, thus providing new avenues for mining novel biomarkers for disease prognosis and diagnosis. Here, we review the current knowledge on DNA methylation biomarkers for the prognostication and non-invasive diagnosis of gastrointestinal cancers and highlight their clinical application.
表观遗传调控的改变是许多人类疾病的中心环节，包括癌症。在过去的二十年中，我们对表观遗传改变在致癌作用中的作用的理解取得了重大进展，特别是在 DNA 甲基化、组蛋白修饰和非编码 RNA 方面。CpG 岛 DNA 的异常高甲基化是介导肿瘤抑制基因转录沉默的一种既定现象，它是胃肠道癌发展的早期事件。因此，异常 DNA 甲基化的检测正被开发为胃肠道癌预后和诊断的生物标志物。不同的组织类型都适合分析甲基化 DNA，如肿瘤组织、血液、血浆和粪便，其中一些标志物已经在临床环境中得到应用。全基因组表观基因组方法的最新进展使癌症甲基组的全面图谱成为可能，从而为挖掘疾病预后和诊断的新型生物标志物提供了新途径。在这里，我们综述了用于预测和非侵入性诊断胃肠道癌的 DNA 甲基化生物标志物的最新知识，并强调了它们的临床应用。
