Division of Digestive and Liver Diseases, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California.
Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, California.
Semin Liver Dis. 2019 Nov;39(4):452-462. doi: 10.1055/s-0039-1688503. Epub 2019 Jun 21.
There is a clear and unmet need for biomarkers in hepatocellular carcinoma (HCC). Circulating cell free deoxyribonucleic acid (cfDNA) is a fragmented DNA subtype, found in the blood circulation. Circulating tumor DNA (ctDNA) is the fraction of total cfDNA, which originates from the primary tumor or metastases in patients with cancer. Earlier studies reported that quantitative measurement cfDNA has diagnostic and prognostic role for HCC. More recently, improvement in next-generation sequencing technology and better understanding of genetic or epigenetic alteration of HCC have allowed comprehensive analysis of mutational and methylation landscape of ctDNA. Hotspot mutation panels and methylation panels have both shown promising performance. None of these tests have yet been validated in longitudinal cohorts for preclinical detection of HCC. In this article, the authors discuss the currently available ctDNA detection technologies, their diagnostic and prognostic performance in HCC, and future research directions.
在肝细胞癌 (HCC) 中，存在明确且未得到满足的生物标志物需求。循环无细胞游离脱氧核糖核酸 (cfDNA) 是一种在血液循环中发现的碎片化 DNA 亚型。循环肿瘤 DNA (ctDNA) 是源自癌症患者原发性肿瘤或转移灶的总 cfDNA 中的一部分。早期研究报告称，定量测量 cfDNA 对 HCC 具有诊断和预后作用。最近，下一代测序技术的改进和对 HCC 遗传或表观遗传改变的更好理解，使得对 ctDNA 的突变和甲基化景观进行全面分析成为可能。热点突变面板和甲基化面板都表现出了有前景的性能。这些检测方法都尚未在用于 HCC 临床前检测的纵向队列中得到验证。在本文中，作者讨论了目前可用的 ctDNA 检测技术，它们在 HCC 中的诊断和预后性能，以及未来的研究方向。
