Laboratory of Rare Human Circulating Cells, University Hospital Center, University of Montpellier, Montpellier, France.
CREEC, MIVEGEC, University of Montpellier, CNRS, IRD, Montpellier, France.
Clin Chem. 2024 Jan 4;70(1):33-48. doi: 10.1093/clinchem/hvad168.
Globally, liver cancers are the second most lethal malignancy after lung cancer (0.83 million deaths in 2020). Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer and is typically associated with liver fibrosis or cirrhosis. HCC diagnosis relies on histologic examination of surgical specimens or conventional tissue biopsy material. However, standard tissue biopsies are invasive and often do not accurately reflect the tumor heterogeneity. On the other hand, the use of liquid biopsies, represented mainly by circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), has greatly increased in the past 2 decades. Indeed, liquid biopsies are a noninvasive, repeatable, and sensitive approach to studying tumor biology.
This review describes current clinical applications of ctDNA analysis in the management of patients with chronic liver disease, cirrhosis, and HCC. There is a substantial clinical potential of ctDNA, but interventional studies are still lacking for the moment.
Detection of ctDNA in both asymptomatic individuals and high-risk patients (with chronic liver disease or cirrhosis) contributes to the early diagnosis of HCC. ctDNA analysis also offer tremendous information on the tumor burden and on the risk of early recurrence. The implementation of ctDNA analysis, in association with classical tumor markers (e.g., alpha-fetoprotein), may improve (a) HCC screening in high-risk patients, (b) stratification of the recurrence risk after surgery, and (c) prognosis evaluation of patients with HCC.
在全球范围内，肝癌是仅次于肺癌的第二大致命恶性肿瘤（2020 年死亡 83 万人）。肝细胞癌（HCC）是原发性肝癌的主要类型，通常与肝纤维化或肝硬化有关。HCC 的诊断依赖于手术标本或常规组织活检材料的组织学检查。然而，标准的组织活检具有侵入性，并且往往不能准确反映肿瘤的异质性。另一方面，过去 20 年来，液体活检（主要代表为循环肿瘤 DNA（ctDNA）和循环肿瘤细胞（CTC））的应用大大增加。事实上，液体活检是一种非侵入性、可重复和敏感的研究肿瘤生物学的方法。
本文描述了 ctDNA 分析在慢性肝病、肝硬化和 HCC 患者管理中的当前临床应用。ctDNA 具有很大的临床应用潜力，但目前仍缺乏干预性研究。
在无症状个体和高危患者（慢性肝病或肝硬化）中检测 ctDNA 有助于 HCC 的早期诊断。ctDNA 分析还提供了有关肿瘤负荷和早期复发风险的大量信息。ctDNA 分析与经典肿瘤标志物（如甲胎蛋白）联合应用，可能改善（a）高危患者的 HCC 筛查，（b）手术后复发风险的分层，以及（c）HCC 患者的预后评估。
