肝癌患者外周血中循环肿瘤细胞数量与肝移植后肿瘤早期复发的相关性研究

Association of the number of circulating tumor cells and early recurrence in patients with hepatocellular carcinoma following liver transplantation

目的探讨肝癌患者外周血中循环肿瘤细胞（CTC）数量与肝移植后肿瘤早期复发的相关性。方法以2013年10月至2014年11月因原发性肝癌行肝移植的42例受者为对象，肝移植前影像学检查均未见肿瘤肝外转移灶，移植后均经病理检查明确原发病的诊断。采用CellSearchSys-tern设备检测患者肝移植前外周血CTC，肝移植后对所有受者随访1年，随访期间记录肿瘤复发和转移情况，用x2检验和Cox风险比例模型分析受者肿瘤的复发时间、临床病理资料与CTC的关系。结果42例受者中肝移植前外周血CTC阴性者13例（31．0%，13／42），呈阳性者29例（69．0％，29／42）。单因素分析显示，CTC的数量与肿瘤分化程度（X2=10．403，P=0．006）和TNM分期（X2=7．119，P=0．005）有关。随访期间，42例受者中有20例复发（其中18例CTC阳性），单因素分析显示，TNM分期（X2=5．599，P=0．010）、CTC数量（X2=6．083，P=0．007）与肝癌早期复发有关。Cox风险比例模型显示，CTC数量可以作为肝癌患者肝移植后预测肿瘤复发时间的独立预后因素，CTC≥1个者的复发时间明显早于CTC阴性者（P〈0．05）。结论肝癌患者肝移植前外周血中检出CTC者，其肝移植后早期易肿瘤复发；CTC可以作为判断肝癌患者肝移植后肿瘤复发时间的独立指标。

Objective To investigate the association of the number of circulating tumor cells （CTCs） and early recurrence in patients with hepatocellular carcinoma （HCC） after liver transplantation. Method A total of 42 patients who received liver transplantation for HCC at Tongji Hospital from October 2013 to November 2014 were enrolled in this study. Extrahepatic tumor metastasis had not been found before liver transplantation by imaging examination, and the primary disease was diagnosed after liver transplantation by pathological examination. Preoperative blood samples from these 42 patients were tested for CTCs by the Cell Search system. All patients were followed up for one year. The tumor recurrence and metastasis in these patients were recorded during the follow-up period. Then X2 test and Cox proportional hazard models were used to analyze the relationship between CTCs and tumor recurrence time, clinicopathologic data. Result In these patients with HCC before liver transplantation, the CTC-positive （CTC≥1） rate was 69% （29/42）, and the negative rate was 31 % （13/42）. Univariate analysis revealed that the number of CTCs was significantly correlated with tumor differentiation grade （X2 = 10. 403, P = 0. 006）, and TNM stages （X2= 7. 119, P = 0. 005）. As to follow-up, HCC recurred in 20 patients （including 18 patients positive for CTCs）. Besides, early tumor recurrence after liver transplantation was related with TNM stages （X2 = 5. 599, P = 0. 010）, and CTCs （X2 = 6. 083, P = 0. 007） by the same analysis. Cox proportional hazard model revealed that CTC was an independent prognostic factor to determine the tumor recurrence time after liver transplantation （P = 0. 046）. The recurrence in patients positive for CTCs was earlier than in those negative for CTCs （P〈0. 05）. Conclusion In the HCC patients withthe preoperative CTC ≥ 1 in peripheral blood, the tumor recurrence is earlier after liver transplantation. Furthermore, CTC can be used as an independent prognostic factor to determine the tumor recurrence time after liver transplantation.