甲基化循环肿瘤DNA的检测及应用

The Detection and Application of Methylated Circulating Tumor DNA

癌症目前仍是医学界面临的第一大难题,其早期诊断、预后风险预测及治疗疗效评估有利于提高患者的生存率。目前临床上诊断癌症主要依靠肿瘤组织病理、内窥镜等检查,但都存在侵入性和异质性的问题。而在肿瘤细胞DNA中发生的分子变化如突变、易位和甲基化等,在循环肿瘤DNA(circulating tumor DNA,ctDNA)中也能反映出来。因此,体液活检检测ctDNA逐渐成为癌症诊断和监测的新方式。DNA甲基化与癌症中许多基因的表达沉默有关,在肿瘤基因组中发现了许多异常的甲基化改变,也有研究证明患者体液中也能检测到甲基化DNA,因此甲基化DNA有望成为新的癌症预测生物标志物。本文拟介绍DNA甲基化与癌症的关系、ctDNA的生物学基础,总结ctDNA的甲基化检测技术,阐述将甲基化ctDNA作为肿瘤生物标志物的作用及研究进展,并提出将ctDNA的甲基化检测应用于临床肿瘤方面的前景和挑战。

Cancer is still one of the biggest challenges medical professionals are currently facing,and the early diagnosis,prognostic prediction and therapeutic efficacy evaluation of cancer can facilitate the survival rate of patients.At present,the diagnosis of cancer mainly relies on tumor histopathology and endoscopy,which are both invasive and with heterogeneity.Molecular alternations in tumor cell DNA,such as mutation,translocation and methylation,can also be reflected in circulating tumor DNA(ctDNA).Therefore,liquid biopsy of ctDNA detection is becoming a new way of cancer diagnosis and monitoring gradually.DNA methylation is associated with the silencing of many genes in tumor,and a large number of abnormal methylation alternations have been found in tumor genomes.Previous studies have also proved that methylated DNA can also be detected in body fluids of cancer patients,so methylated DNA is expected to be the new biomarker for cancer prediction.This paper intends to introduce the association between DNA methylation and cancer,and the biological basis of ctDNA,summarize the detecting technologies of ctDNA methylation,expound the role of ctDNA as a tumor biomarker and related research progresses,also propose the prospect and challenge of applying ctDNA methylation detection to clinical tumors.