Hepatoblastoma is characterized by driver mutations inCTNNB1, making it an attractive biomarker for a liquid biopsy approach utilizing circulating tumor DNA (ctDNA). This prospective observational study sought to ascertain the feasibility of ctDNA detection in patients with hepatoblastoma and explore its associations with established clinical indicators and biomarkers, including serum Alpha-fetoprotein (AFP). We obtained 38 plasma samples and 17 tumor samples from 20 patients with hepatoblastoma. These samples were collected at various stages: 10 at initial diagnosis, 17 during neoadjuvant chemotherapy, 6 post-operatively, and 5 at disease recurrence. Utilizing a bespoke sequencing assay we developed called QUENCH, we identified single nucleotide variants and deletions inCTNNB1ctDNA. Our study demonstrated the capability to quantitate ctDNA down to a variant allele frequency of 0.3%, achieving a sensitivity of 90% for patients at initial diagnosis, and a specificity of 100% at the patient level. Notably, ctDNA positivity correlated with tumor burden, and ctDNA levels exhibited associations with macroscopic residual disease and treatment response. Our findings provide evidence for the utility of quantitative ctDNA detection in hepatoblastoma management. Given the distinct detection targets, ctDNA and AFP-based stratification and monitoring approaches could synergize to enhance clinical decision-making. Further research is needed to elucidate the interplay between ctDNA and AFP and determine the optimal clinical applications for both methods in risk stratification and residual disease detection.
肝母细胞瘤以CTNNB1基因驱动突变为特征，这使其成为利用循环肿瘤DNA（ctDNA）进行液体活检的理想生物标志物。本前瞻性观察性研究旨在明确肝母细胞瘤患者ctDNA检测的可行性，并探讨其与血清甲胎蛋白（AFP）等既定临床指标及生物标志物的关联。我们从20例肝母细胞瘤患者中获取了38份血浆样本和17份肿瘤样本，样本采集涵盖不同阶段：初诊时10份、新辅助化疗期间17份、术后6份以及疾病复发时5份。通过我们自主研发的QUENCH测序技术，我们在CTNNB1 ctDNA中检测到单核苷酸变异和缺失。研究证明该技术可将ctDNA定量检测下限扩展至等位基因频率0.3%，在初诊患者中达到90%的灵敏度，患者层面特异性达100%。值得注意的是，ctDNA阳性状态与肿瘤负荷相关，其水平变化与肉眼残留病灶及治疗反应存在显著关联。本研究为ctDNA定量检测在肝母细胞瘤临床管理中的应用提供了实证依据。鉴于检测靶标的差异性，ctDNA与AFP分层监测策略可形成协同效应以优化临床决策。未来需进一步阐明ctDNA与AFP的相互作用机制，并探索这两种方法在风险分层和残留病灶检测中的最佳临床应用模式。
Quantitative ctDNA Detection in Hepatoblastoma: Implications for Precision Medicine
肿瘤(癌症)患者之家