Clinical Utility and Future Perspectives of Circulating Tumor DNA in Hepatocellular Carcinoma

肝细胞癌(Hepatocellular carcinoma, HCC)作为最常见的原发性肝癌，也是世界范围内最常见的癌症相关死亡的原因之一。由于HCC潜伏期较长、诊断阶段较晚及对全身治疗不敏感，到目前为止，肝脏活检和手术切除仍是临床决策的金标准。传统活检可提供肿瘤生物学信息，但其侵入性高，样本量少，无法代表肿瘤异质性或监测动态肿瘤进展，因此迫切需要微创或无创的新诊断策略以便早期诊断HCC并监测肿瘤进展。近年来，“液体活检(Liquid biopsy)”的概念引起了广泛关注，其无创、可重复分析的特性可实时监测肿瘤复发、转移或治疗反应。随着高灵敏度液体活检技术的发展，HCC循环肿瘤细胞(circulating tumor cells, CTCs)、循环肿瘤DNA (circulating tumor DNA, ctDNA)以及肿瘤来源的外泌体等检测和分析的发展前景可观。本综述重点介绍ctDNA检测及其作为HCC诊断、预后和监测的无创生物标志物的临床应用及展望。Hepatocellular carcinoma (HCC) is the most common primary liver cancer and one of the leading causes of cancer-related deaths worldwide. Due to its long latency period, late-stage diagnosis, and insensitivity to systemic therapies, conventional tissue biopsy and surgical resection remain the gold standards for clinical decision-making to date. Although traditional biopsy can provide tumor biology, it is imperative to find non-invasive diagnostic strategy for early detection and monitoring of HCC due to its invasive nature, limited sample size, and inability to represent tumor heterogeneity or monitor dynamic tumor progression. In recent years, a new concept of “liquid biopsy” has emerged with significant attention due to its non-invasive and repeatable analysis capabilities, enabling real-time monitoring of tumor recurrence, metastasis, or treatment response. With advancements in high-sensitivity liquid biopsy technologies, the detection and analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and tumor-derived exosomes in HCC have shown promising prospects. The ctDNA detection and its clinical applications and future potential as a non-invasive biomarker for the diagnosis, prognosis, and monitoring of HCC are highlighted in this review.