肝细胞癌术前循环肿瘤细胞与微血管侵犯关系的临床研究

Clinical study on the correlation between preoperative circulating tumor cells and microvascular invasion in hepatocellular carcinoma

目的探讨肝细胞癌患者术前外周血循环肿瘤细胞(CTC)与微血管侵犯(MVI)的相关性。方法回顾性分析2018年1月至2020年3月在中山大学附属中山医院行肝细胞癌切除术的227例患者资料,术前通过Cyttel法检测患者的CTC。分析术前外周血CTC与患者临床特征的关系;采用多因素logistic回归模型分析MVI的独立危险因素;采用受试者工作特征(ROC)曲线比较各独立危险因素预测MVI发生的效能,明确CTC与MVI的关系。结果根据ROC曲线,预测MVI的CTC、甲胎蛋白(AFP)、维生素K缺乏或拮抗剂Ⅱ诱导的蛋白(PIVKA-Ⅱ)、肿瘤长径分界值分别为3个/3.2 ml、158 μg/L、178 AU/L及59 mm。以外周血CTC≥3个/3.2 ml为阳性组,<3个/3.2 ml为阴性组,两组分别有117、110例。术前CTC阳性组与阴性组中位AFP水平分别为123.0 μg/L(0~20 000.0 μg/L)、9.6 μg/L (0~18 676.0 μg/L),中位肿瘤长径分别为50.0 mm(5.0~200.0 mm)、36.0 mm(2.0~150.0 mm),两组间差异均有统计学意义(均P<0.05)。术前,AFP≥158 μg/L(OR=3.551,95%CI 1.426~8.843,P=0.006)、PIVKA-Ⅱ≥178 AU/L(OR=12.250,95%CI 4.384~34.231,P<0.01)、外周血CTC≥3个/3.2 ml(OR=8.913,95%CI 3.561~22.306,P<0.01)及肿瘤长径≥59 mm(OR=3.250,95%CI 1.339~7.885,P=0.009)是MVI发生的独立危险因素;它们预测MVI的ROC曲线下面积(AUC)分别为0.752、0.777、0.857、0.743,CTC预测MVI的效能高于AFP、肿瘤长径,差异均有统计学意义(均P<0.05),CTC预测MVI的效能略高于PIVKA-Ⅱ,但差异无统计学意义(P>0.05)。结论 CTC可能是临床提示肝细胞癌MVI的重要指标之一。

Objective To investigate the correlation between preoperative circulating tumor cells(CTC)and microvascular invasion(MVI)in patients with hepatocellular carcinoma.Methods The data of 227 patients who underwent hepatocellular carcinoma resection in Zhongshan Hospital Affiliated to Sun Yat-sen University from January 2018 to March 2020 were retrospectively analyzed.The peripheral blood CTC was detected by Cyttel detection before operation.The relationship between preoperative peripheral blood CTC and clinical characteristics of patients was analyzed;the multivariate logistic regression model was used to analyze the independent risk factors for MVI;the receiver operating characteristic(ROC)curve was used to compare the efficacy of each independent risk factor in predicting the occurrence of MVI,and the relationship between CTC and MVI was clarified.Results According to the ROC curve,the cut-off values for predicting MVI of CTC,alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonistⅡ(PIVKA-Ⅱ),and tumor long-axis diameter were 3 CTC/3.2 ml,158μg/L,178 AU/L and 59 mm.CTC-positive group had≥3 CTC/3.2 ml in peripheral blood,and CTC-negative group had<3 CTC/3.2 ml,and there were 117 and 110 cases in the two groups.The median AFP levels of preoperative CTC-positive group and CTC-negative group were 123.0μg/L(0-20000.0μg/L)and 9.6μg/L(0-18676.0μg/L),and the median tumor long-axis diameter was 50.0 mm(5.0-200.0 mm)and 36.0 mm(2.0-150.0 mm),the differences between the two groups were statistically significant(both P<0.05).Before operation,AFP≥158μg/L(OR=3.551,95%CI 1.426-8.843,P=0.006),PIVKA-Ⅱ≥178 AU/L(OR=12.250,95%CI 4.384-34.231,P<0.01),peripheral blood CTC≥3 CTC/3.2 ml(OR=8.913,95%CI 3.561-22.306,P<0.01)and tumor long-axis diameter≥59 mm(OR=3.250,95%CI 1.339-7.885,P=0.009)were independent risk factors for the occurrence of MVI;the area under the ROC curve(AUC)of these factors for predicting MVI was 0.752,0.777,0.857 and 0.743.CTC was more effective in predicting MVI than AFP and tumor long-axis diameter,and the differences were statistically significant(both P<0.05).The efficacy of CTC in predicting MVI was slightly better than that of PIVKA-Ⅱ,but the difference was not statistically significant(P>0.05).Conclusion CTC may be one of the important indicators of hepatocellular carcinoma MVI in clinical practice.