Li Lei, Fu Kai, Zhou Wenyu, Snyder Michael
Department of Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, USA.
Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, 37 Guoxuexiang, Chengdu, China.
Precis Clin Med. 2019 Mar;2(1):45-56. doi: 10.1093/pcmedi/pbz003. Epub 2019 Mar 15.
Lung cancer is the leading cause of cancer-related deaths worldwide. Low dose computed tomography (LDCT) is commonly used for disease screening, with identified candidate cancerous regions further diagnosed using tissue biopsy. However, existing techniques are all invasive and unavoidably cause multiple complications. In contrast, liquid biopsy is a noninvasive, ideal surrogate for tissue biopsy that can identify circulating tumor DNA (ctDNA) containing tumorigenic signatures. It has been successfully implemented to assist treatment decisions and disease outcome prediction. ctDNA methylation, a type of lipid biopsy that profiles critical epigenetic alterations occurring during carcinogenesis, has gained increasing attention. Indeed, aberrant ctDNA methylation occurs at early stages in lung malignancy and therefore can be used as an alternative for the early diagnosis of lung cancer. In this review, we give a brief synopsis of the biological basis and detecting techniques of ctDNA methylation. We then summarize the latest progress in use of ctDNA methylation as a diagnosis biomarker. Lastly, we discuss the major issues that limit application of ctDNA methylation in the clinic, and propose possible solutions to enhance its usage.
肺癌是全球癌症相关死亡的主要原因。低剂量计算机断层扫描（LDCT）通常用于疾病筛查，对识别出的候选癌区通过组织活检做进一步诊断。然而，现有技术均具有侵入性，且不可避免地会引发多种并发症。相比之下，液体活检是一种非侵入性的理想组织活检替代方法，它能够识别出含有致瘤特征的循环肿瘤DNA（ctDNA）。它已成功用于辅助治疗决策和疾病预后预测。ctDNA甲基化作为一种液体活检方式，可分析致癌过程中发生的关键表观遗传改变，越来越受到关注。事实上，异常ctDNA甲基化在肺恶性肿瘤的早期阶段就会出现，因此可用作肺癌早期诊断的替代方法。在本综述中，我们简要概述了ctDNA甲基化的生物学基础和检测技术。然后，我们总结了将ctDNA甲基化用作诊断生物标志物的最新进展。最后，我们讨论了限制ctDNA甲基化在临床应用的主要问题，并提出了可能的解决方案以促进其应用。
