DNA甲基化生物标记物在恶性肿瘤中的转化应用

Translational application of DNA methylation biomarkers in malignant tumors

肿瘤的发生发展存在广泛的遗传变化和相关的基因功能及活动失调。其中表观遗传学中DNA甲基化是表征最好的表观遗传修饰之一,它影响基因表达和基因组稳定性,对肿瘤的发生发展具有重要影响。这些表观遗传变化大部分发生在肿瘤的早期,且在整个肿瘤类型中普遍存在,DNA甲基化标记物是肿瘤早期诊断、预后和治疗检测的重要方法。通过血液、粪便、尿液和其他生物样本中可以检测癌症相关的DNA甲基化变化,它是一种无创、快速和可重复的组织活检的替代方法。DNA甲基化是可适用于人群筛查的简单、经济和高度特异性的癌症检测的重要手段,虽然面临许多挑战,但是DNA甲基化生物标记物以独特的优势,具有临床转化应用的前景和价值。本文综述了DNA甲基化特征、作用机制,及在膀胱癌、乳腺癌、结直肠癌等肿瘤中的早期诊断、临床治疗效果及预后判定的最新研究进展,并讨论了临床转化存在的问题和展望。

Extensive genetic changes as well as related gene function and activity disorders occur in the development of malignant tumors.DNA methylation in epigenetics is one of the best-characterized epigenetic modifications.It affects gene expression and genome stability,having an important impact on the development of malignant tumors.Most of these epigenetic changes occur in the early stages of malignant tumors and are widespread in the entire malignant tumor.DNA methylation biomarkers are important methods for early tumor diagnosis,prognosis and treatment detection.Cancer-related DNA methylation changes can be detected in blood,feces,urine and other biological samples.It is a non-invasive,rapid and reproducible alternative to tissue biopsy.DNA methylation is a simple,economical and highly specific malignant tumor detection method that can be applied to population screening.Although it faces many challenges,DNA methylation biomarkers have unique advantages,having the prospect of clinical translational application and value.This article reviews the characteristics of DNA methylation,the mechanism of action as well as the latest research progress in early diagnosis,clinical treatment effects,and prognosis determination in bladder cancer,breast cancer,colorectal cancer and other malignant tumors,discussing the problems and prospects of clinical translation.