Division of Surgery, John Hunter Hospital, Newcastle, New South Wales, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
Division of Surgery, John Hunter Hospital, Newcastle, New South Wales, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, Australia.
J Surg Res. 2019 Apr;236:184-197. doi: 10.1016/j.jss.2018.11.029. Epub 2018 Dec 21.
Circulating tumour DNA (ctDNA) has emerged as an excellent candidate for the future of liquid biopsies for many cancers. There has been growing interest in blood-based liquid biopsy because of the potential of ctDNA to produce a noninvasive test that can be used for: the diagnosis of colorectal cancer, monitoring therapy response, and providing information on overall prognosis. The aim of this review was to collate and explore the current evidence regarding ctDNA as a screening tool for colorectal cancer (CRC).
A systematic review of published articles in English over the past 20 y was performed using Medline, Embase, and Cochrane databases on May 23, 2017. After a full-text review, a total of 69 studies were included. Two assessment tools were used to review and compare the methodological quality of these studies.
Among the 69 studies included, 17 studies reviewed total cfDNA, whereas six studies looked at the DNA integrity index and 15 focused on ctDNA. There were a total of 40 studies that reviewed methylated cfDNA with 19 of these focussing specifically on SEPT9.
The results of this review indicate that methylated epigenetic ctDNA markers are perhaps the most promising candidates for a blood-based CRC-screening modality using cell-free (cf) DNA. Methylated cfDNA appears to be less specific for CRC compared to ctDNA; however, they have demonstrated good sensitivity for early-stage CRC. Further research is required to determine which methylated cfDNA markers are the most accurate when applied to large cohorts of patients. In addition, reliable comparison of results across multiple studies would benefit from standardization of methodology for DNA extraction and PCR techniques in the future.
循环肿瘤 DNA（ctDNA）已成为许多癌症未来液体活检的优秀候选者。由于 ctDNA 具有产生非侵入性测试的潜力，该测试可用于：结直肠癌的诊断、监测治疗反应，并提供总体预后信息，因此对基于血液的液体活检越来越感兴趣。本综述的目的是整理和探讨目前关于 ctDNA 作为结直肠癌（CRC）筛查工具的证据。
使用 Medline、Embase 和 Cochrane 数据库于 2017 年 5 月 23 日对过去 20 年发表的英文文章进行了系统综述。经过全文审查，共纳入 69 项研究。使用两种评估工具对这些研究的方法学质量进行了回顾和比较。
在纳入的 69 项研究中，有 17 项研究回顾了总 cfDNA，6 项研究检查了 DNA 完整性指数，15 项研究集中在 ctDNA 上。共有 40 项研究审查了甲基化 cfDNA，其中 19 项专门研究了 SEPT9。
本综述的结果表明，甲基化表观遗传 ctDNA 标志物可能是基于无细胞（cf）DNA 的 CRC 筛查方法中最有前途的候选者。与 ctDNA 相比，甲基化 cfDNA 对 CRC 的特异性较低；然而，它们对早期 CRC 具有良好的敏感性。需要进一步的研究来确定在大量患者群体中应用哪些甲基化 cfDNA 标志物最准确。此外，未来需要标准化 DNA 提取和 PCR 技术的方法，以促进多个研究结果的可靠比较。
