METHODS: Plasma samples were obtained from patients with HCC prior to surgery, locoregional or systemic therapy, and were analyzed by ULP-WGS of cfDNA to an average genome-wide fold coverage of 0.3x. ctDNA and copy number alterations (CNA) were estimated using the software package ichorCNA.
RESULTS: Samples were obtained from 73 HCC patients at different BCLC stages (BCLC 0/A: n=37, 50.7%; BCLC B/C: n=36, 49.3%). ctDNA was detected in 18 out of 31 patients who received systemic treatment. Patients with detectable ctDNA showed significantly worse overall survival (median, 13.96 months vs not reached). ctDNA remained an independent predictor of prognosis after adjustment by clinical-pathologic features and type of systemic treatment (hazard ratio 7.69; 95%, CI 2.09-28.27). Among ctDNA-positive patients under systemic treatments, the loss of large genomic regions in 5q and 16q arms was associated with worse prognosis after multivariate analysis.
CONCLUSIONS: ULP-WGS of cfDNA provides clinically relevant information about the tumor biology. The presence of ctDNA and the loss of 5q and 16q arms in ctDNA-positive patients are independent predictors of worse prognosis in patients with advanced HCC receiving systemic therapy.
■手术前从肝癌患者获得血浆样本,局部或全身治疗,并通过cfDNA的ULP-WGS分析至0.3x的平均全基因组倍数覆盖率。使用软件包ichorCNA估计ctDNA和拷贝数改变(CNA)。
■样本来自73例不同BCLC分期的HCC患者(BCLC0/A:n=37,50.7%;BCLCB/C:n=36,49.3%)。在接受全身治疗的31例患者中,有18例检测到ctDNA。具有可检测的ctDNA的患者显示出明显更差的总体生存率(中位数,13.96个月vs未达到)。通过临床病理特征和全身治疗类型调整后,ctDNA仍然是预后的独立预测因子(风险比7.69;95%,CI2.09-28.27)。在接受系统治疗的ctDNA阳性患者中,多变量分析后,5q和16q组的大基因组区域丢失与预后较差相关.
■cfDNA的ULP-WGS提供了有关肿瘤生物学的临床相关信息。ctDNA的存在以及ctDNA阳性患者中5q和16q臂的丢失是在系统治疗下晚期HCC患者预后较差的独立预测因子。