Circulating cell-free DNA (cfDNA) has emerged as a compelling candidate of liquid biopsy markers for the diagnosis and prognosis of several cancers. We systematically reviewed data on the role of cfDNA markers in the diagnosis, prognosis and treatment of hepatocellular carcinoma (HCC). Early studies suggested that levels of circulating cfDNA, mitochondrial DNA and cfDNA integrity are higher in patients with HCC than chronic liver diseases. In subsequent studies, methylation changes in circulating tumor DNA (ctDNA) as well as cfDNA fragmentation patterns and circulating nucleosomes were found to offer high sensitivity (>60%) and excellent specificity (>90%) for HCC diagnosis. The predictive role of cfDNA markers and ctDNA has been assessed in a few studies including untreated patients with HCC providing promising results for prediction of survival. However, port-hepatectomy detection of cfDNA/ctDNA markers or copy number variation indicators of cfDNA seem to reflect minimum residual disease and thus a high risk for HCC recurrence. The same markers can be useful for prediction after transarterial chemoembolization, radiofrequency ablation, radiotherapy and even systemic therapies. In conclusion, cfDNA markers can be useful in HCC surveillance, improving early diagnosis rates, as well as for monitoring treatment effectiveness and minimal residual disease post-treatment.
循环游离DNA（cfDNA）已成为多种癌症诊断和预后液体活检标志物的有力候选者。本文系统综述了cfDNA标志物在肝细胞癌（HCC）诊断、预后及治疗中的作用。早期研究表明，HCC患者外周血中循环cfDNA、线粒体DNA水平及cfDNA完整性均高于慢性肝病患者。后续研究发现，循环肿瘤DNA（ctDNA）甲基化改变、cfDNA片段化模式及循环核小体对HCC诊断具有较高敏感性（>60%）和优异特异性（>90%）。已有少数研究在未经治疗的HCC患者中评估了cfDNA标志物及ctDNA的预测价值，其在生存预测方面展现出良好前景。然而，肝切除术后cfDNA/ctDNA标志物或cfDNA拷贝数变异指标的检测，似乎能反映微小残留病灶，从而提示较高的HCC复发风险。这些标志物同样可用于经动脉化疗栓塞、射频消融、放疗乃至全身治疗后的预后预测。综上所述，cfDNA标志物在HCC监测、提高早期诊断率以及评估治疗效果和术后微小残留病灶方面具有重要应用价值。
The Current Role of Circulating Cell-Free DNA in the Management of Hepatocellular Carcinoma
肿瘤(癌症)患者之家