肝癌肝移植术前循环肿瘤细胞检测的预后价值

目的研究分析肝移植术前循环肿瘤细胞(CTC)检测评估预测受者肝癌复发与生存的应用价值。方法收集中山大学附属中山医院于2015年10月至2019年10月期间62例肝癌患者肝移植术前通过Cyttel法检测分析CTC,应用X-tile软件通过Kaplan-Meier法确定术前CTC最佳的截止值,并分析CTC与临床因素的关系;单因素及多因素COX回归分析影响其预后的独立危险因素,采用Kaplan-Meier法描绘肝移植术后无瘤生存期和总生存期的生存曲线。结果确定术前CTC最佳临界值为3个/3.2 ml,将CTC≥3/3.2 mL设置为CTC阳性组,CTC<3个/3.2 ml设置为CTC阴性组;肝移植术前CTC阳性/阴性与术前甲胎蛋白(AFP)水平、最大肿瘤直径、淋巴转移、肝移植标准、分化程度呈显著相关(P<0.05);单因素及多因素COX回归模型法系发现术前CTC个数(HR:1.262,95%CI:1.069~1.489,P=0.006)、微血管侵犯(HR:2.657,95%CI:1.120~6.305,P=0.027)是肝癌肝移植术后无瘤生存期的独立危险因素,而微血管侵犯(HR:3.738,95%CI:1.219-11.459,P=0.027)是影响肝癌肝移植术后总生存期唯一的独立危险因素;术前CTC阳性/阴性与肿瘤复发或转移(未复发、肝内复发与远处转移)差异有统计学意义(χ²=7.790,P=0.020);术前CTC阴性、阳性患者在1年、2年、3年无瘤生存率分别为82.90%、68.70%、58.90%和49.00%、29.40%、22.10%;术前CTC阴性、阳性患者在1年、2年、3年总生存率为85.50%、77.10%、69.79%和64.90%、47.20%、40.50%。术前CTC阴性的无瘤生存率曲线高于CTC阳性,差异有统计学意义(P=0.001);术前CTC阴性的总生存率曲线高于CTC阳性,差异有统计学意义(P=0.005)。结论术前CTC检测对评估肝癌肝移植术后预后具有重要的临床意义及应用前景。

Prognostic value of detecting circulating tumor cells before liver transplantation for hepatocellular carcinoma

Objective To explore the application value of detecting circulating tumor cells(CTC)before liver transplantation for predicting the recurrence and survival of hepatocellular carcinoma(HCC).Methods From October 2015 to October 2019,62 HCC patients at Affiliated Zhongshan Hospital were collected and analyzed by Cyttel method before liver transplantation.CTC was determined by X-tile software and Kaplan-Meier method for determining the optimal cutoff value of CTC before liver transplantation and the relationship between CTC and clinical factors was analyzed.Univariate and multivariate COX regression analyses were performed for determining the independent risk factors affecting the prognosis.Kaplan Meier method was employed for describing the survival curve of tumor-free survival and overall survival after transplantation.Results The optimal preoperative critical value of CTC was 3.2 ml.CTC≥3/3.2 mL was set as CTC positive group while CTC<3/3.2 mL CTC negative group.The positive/negative CTC before transplantation was significantly correlated with preoperative Alpha-fetoprotein(AFP)level,maximal tumor diameter,lymph node metastasis,liver transplantation criteria and degree of differentiation(P<0.05).Univariate and multivariate COX regression models indicated that the number of preoperative CTC(HR:1.262,95%CI:1.069-1.489,P=0.006)and microvascular invasion(HR:2.657,95%CI:1.120-6.305,P=0.027)were independent risk factors for tumor-free survival after transplantation while microvascular invasion(HR:3.738,95%CI:1.219-11.459,P=0.027)was the sole independent risk factor affecting the overall survival of HCC after transplantation.Statistically significant difference existed between preoperative CTC positive/negative and tumor recurrence or metastasis(no recurrence,intrahepatic recurrence,and distant metastasis)(χ²=7.790,P=0.020).The disease-free survival rates of 1/2/3-year CTC-negative/positive patients were 82.90%,68.70%,58.90%and 49.00%,29.40%,22.10%;the 1/2/3-year overall survival rates of preoperative CTC-negative/positive patients were 85.50%,77.10%,69.79%and 64.90%,47.20%,40.50%respectively.The disease-free survival curve of CTC-negative patients was significantly higher than that of CTC-positive counterparts(P<0.001)and the overall survival curve of CTC-negative patients was significantly higher than that of CTC-positive counterparts(P<0.005).Conclusions Preoperative CTC detection has certain application value in evaluating the prognosis of liver cancer after liver transplantation,which has important clinical significance and application prospects.