Driskill Graduate Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Dr., Suite 1400, Chicago, IL, 60611, USA.
Cancer Commun (Lond). 2019 Mar 29;39(1):12. doi: 10.1186/s40880-019-0356-x.
Robust and clinically convenient biomarkers for cancer diagnosis, early detection, and prognosis have great potential to improve patient survival and are the key to precision medicine. The advent of next-generation sequencing technologies enables a more sensitive and comprehensive profiling of genetic and epigenetic information in tumor-derived materials. Researchers are now able to monitor the dynamics of tumorigenesis in new dimensions, such as using circulating cell-free DNA (cfDNA) and tumor DNA (ctDNA). Mutation-based assays in liquid biopsy cannot always provide consistent results across studies due partly to intra- and inter-tumoral heterogeneity as well as technical limitations. In contrast, epigenetic analysis of patient-derived cfDNA is a promising alternative, especially for early detection and disease surveillance, because epigenetic modifications are tissue-specific and reflect the dynamic process of cancer progression. Therefore, cfDNA-based epigenetic assays are emerging to be a highly sensitive, minimally invasive tool for cancer diagnosis and prognosis with great potential in future precise care of cancer patients. The major obstacle for applying epigenetic analysis of cfDNA, however, has been the lack of enabling techniques with high sensitivity and technical robustness. In this review, we summarized the advances in epigenome-wide profiling of 5-hydroxymethylcytosine (5hmC) in cfDNA, focusing on the detection approaches and potential role as biomarkers in different cancer types.
用于癌症诊断、早期检测和预后的稳健且临床方便的生物标志物具有改善患者生存的巨大潜力，是精准医学的关键。下一代测序技术的出现使人们能够更敏感、更全面地分析肿瘤来源材料中的遗传和表观遗传信息。研究人员现在能够从新的维度监测肿瘤发生的动态，例如使用循环无细胞 DNA（cfDNA）和肿瘤 DNA（ctDNA）。基于突变的液体活检检测在不同研究中并不总能提供一致的结果，部分原因是肿瘤内和肿瘤间异质性以及技术限制。相比之下，患者衍生 cfDNA 的表观遗传分析是一种很有前途的替代方法，特别是用于早期检测和疾病监测，因为表观遗传修饰是组织特异性的，反映了癌症进展的动态过程。因此，基于 cfDNA 的表观遗传检测作为一种高灵敏度、微创的癌症诊断和预后工具正在兴起，在未来癌症患者的精准护理中具有巨大的潜力。然而，cfDNA 表观遗传分析的主要障碍是缺乏具有高灵敏度和技术稳健性的使能技术。在这篇综述中，我们总结了 cfDNA 中 5-羟甲基胞嘧啶（5hmC）的全基因组图谱分析的进展，重点介绍了不同癌症类型中检测方法和作为生物标志物的潜在作用。
