Abstract: Objective This study was conducted to investigate the value of ctDNA derived from peripheral blood in predicting microvascular invasion （MVI） of HCC. Methods The retrospective case-control study was performed, and the patients with a diagnosis of HCC from Peking University Hospital were enrolled, whose clinical data related to tumor and the peripheral blood ctDNA were collected. The MVI was diagnosed by the pathological analysis of the tumor specimens collected intraoperatively. Results Fifty-nine patients were enrolled in this study, including 37 cases with MVI and 22 cases without MVI. The independent risk factors related to MVI were analyzed by univariate analysis and multivariate analysis with the Logistic retrospective model. Result of receiver operating characteristic curve （ROC）： the cut-off value of ctDNA score level in predicting microvascular invasion of HCC was 0.80, and the area under curve was 0.813. The analysis of influencing factors for microvascular invasion： univariate analysis： ALT>40 U/L, higher TNM, BCLC stage, larger tumor size （>3.5 cm） and ctDNA >0.80 were related to MVI in HCC. And multiple-factor analysis showed that ctDNA >0.80, larger tumor size（>3.5 cm） and late TNM stage were independent risk factors for the development of MVI. The nomogram constructed based on these screened risk factors directly predicted the risk of MVI in HCC patients. Comparison of clinical data of different levels of HCC patient： 59 HCC patients were divided into low ctDNA score group of 32 cases and high ctDNA group of 27 cases based on the cut-off value of ctDNA score. And the case of AFP>400 ng/mL, TBIL>12 μmol/L, APTT>39.5 s, PIVKA-II>40 mAU/mL, the largest size of tumor >3.5 cm and microvascular invasion respectively were significant differenct in the above indicators between these two groups. Conclusion The preoperative ctDNA derived from peripheral blood can be used to predict the preoperative microvascular invasion in HCC, and has a reference significance to the preoperative individualized treatment.

Key words: ctDNA, hepatocellular carcinoma, microvascular invasion, predicting value

摘要： 目的 探讨术前外周血中采集的ctDNA针对肝细胞肝癌（HCC）病人的微循环血管浸润（MVI）是否存在预测价值。方法 收集59例来自北京大学深圳医院的确诊原发性肝癌的患者,术前一周内收集所有患者肿瘤相关术前的临床资料以及外周血ctDNA;术中采集患者的肿瘤标本进行病理分析判断有无MVI发生。采用logistic回归模型进行单因素和多因素分析确定影响MVI的独立危险因素。结果 在59例纳入研究队列的患者中,MVI阳性的患者有37例,MVI阴性患者有22例。采用受试者工作特性曲线（ROC）分析显示：ctDNA预测肝癌MVI发生的最佳截断值为0.80,曲线下面积为0.813,影响肝癌发生的危险因素分析：单因素分析显示：ALT>40 U/L,较晚的TNM、BCLC分期,肿瘤最大径>3.5 cm和ctDNA >0.80与肝癌MVI的发生有关。多因素分析显示：ctDNA>0.80、肿瘤最大径>3.5 cm、较晚的TNM分期,是影响肝癌MVI发生的独立危险因素。根据筛选出的危险因素建立列线图可更加直观的反应肝癌患者MVI的风险因素。比较不同水平ctDNA评分下的肝癌患者的临床特征的不同：根据ctDNA评分的最佳截断值将59例患者分为32例低ctDNA评分组及27例高ctDNA患者组,其中AFP>400 ng/mL、TBIL>12 μmol/L、APTT>39.5 s、PIVKA-II>40 mAU/mL、肿瘤最大径>3.5 cm及微血管侵犯阳性的患者在两组中的差异具有统计学意义。结论 术前外周血ctDNA可用于肝癌MVI的预测,并且对于肝癌患者的患者术前患者精准治疗提供参考。

关键词: 循环肿瘤DNA, 肝细胞肝癌, 微循环血管侵犯, 预测价值