Research on the relationship between Foxp3+ Regulatory T cell and tumor recurrence of patients after liver transplantation for hepatocellular carcinoma
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摘要:
目的 探讨Foxp3+调节性T细胞(Treg)与超加利福尼亚大学洛杉矶分校(UCSF)标准肝细胞癌(肝癌)肝移植患者术后肿瘤复发的关系。 方法 回顾性分析2010年1月至2013年12月在解放军第309医院全军器官移植研究所接受肝移植的24例肝癌患者的临床资料。在随访期内肿瘤复发4例(肿瘤复发组), 余20例无复发(肿瘤未复发组); 以同期健康人的血液标本为对照组。比较肿瘤复发组和肿瘤未复发组术前、术后不同时点甲胎蛋白(AFP)水平; 比较肿瘤复发组和肿瘤未复发组术前、术后不同时点及对照组的Foxp3+Treg(Foxp3+Treg%)水平; 对术前与术后Foxp3+Treg表达与AFP、CD3+和CD8+T水平的关系进行相关分析。 结果 与术前及正常水平相比, 肿瘤未复发组患者术后Foxp3+Treg表达经历先降低后逐渐升高最终稳定于较低水平。与肿瘤未复发组患者比较, 肿瘤复发组患者的AFP和Foxp3+Treg显著升高, 明显高于术前及正常水平(均为P < 0.01), 而且在肿瘤复发组患者中Foxp3+Treg早期异常性升高先于AFP。相关性分析提示, Foxp3+Treg与AFP变化一致, 呈正相关(P < 0.01);而与效应性T细胞(CD3+T细胞、CD8+ T细胞)表达变化相反, 呈负相关(P < 0.05~0.01), 提示Foxp3+Treg与肝癌肝移植术后肿瘤的复发具有密切关系。 结论 Foxp3+Treg与肝癌肝移植术后肿瘤复发的关系密切。超UCSF标准的肝癌肝移植患者术后Foxp3+Treg越高, 提示复发风险越大, 联合检测AFP有助于及早发现肿瘤复发。 Abstract:Objective To discuss the relationship between Foxp3+regulatory T cell(Treg) and tumor recurrence of patients after liver transplantation for primary hepatocellular carcinoma (HCC) over University of California, San Francisco (UCSF) criteria. Methods Clinical data of 24 patients with HCC undergoing liver transplantation in the Organ Transplantation Research Institute of the 309th Hospital of People's Liberation Army from January 2010 to December 2013 were retrospectively studied. During the follow-up, 4 patients recurred (tumor recurrence group) and other 20 patients did not recur (tumor non-recurrence group). The blood samples of healthy people was selected as control group at the same period. The levels of alpha-fetoprotein (AFP) were compared at different time points of the recurrence group and the non-recurrent group before and after transplantation. The levels of Foxp3+Treg (Foxp3+Treg%) were compared at different time points of the tumor recurrence group, the tumor non-recurrence group and the control group before and after transplantation. The relations between expression of Foxp3+Treg and the levels of AFP, CD3+ and CD8+T before and after transplantation were analyzed by correlation analysis. Results Compared with the level of Foxp3+Treg before transplantation and the normal level, the expression of Foxp3+Treg of patients in tumor non-recurrence group after transplantation firstly decreased, then gradually increased and finally stabilized at a low level. Compared with patients in tumor non-recurrence group, the levels of AFP and Foxp3+Treg of patients in tumor recurrence group increased obviously and were significantly higher than the normal levels (both in P < 0.01). Moreover, abnormal increase of Foxp3+Treg at early stage was prior to AFP among the patients in tumor recurrence group. Correlation analysis indicated that the change of Foxp3+Treg was consistent with the changes of AFP, which was positively correlated (P < 0.01). But the change of Foxp3+Treg was contrary to the change of effector T cells (CD3+T cells and CD8+ T cells), which was negatively correlated (P < 0.05-0.01). It indicated that Foxp3+Treg was closely associated with tumor recurrence after liver transplantation for HCC. Conclusions Foxp3+Treg is closely associated with tumor recurrence after liver transplantation for HCC. In the patients after liver transplantation for HCC over UCSF criteria, the higher Foxp3+Treg is, the higher the recurrence risk is. Joint detection of AFP is beneficial to find tumor recurrence. -
Key words:
- Regulatory T cell /
- Hepatocellular carcinoma /
- Liver transplantation /
- Tumor recurrence /
- Prognosis
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图 1 肝癌肝移植术后肿瘤复发患者甲胎蛋白的变化趋势
Figure 1. The changes of AFP of patients with tumor recurrence after liver transplantation for hepatocellular carcinoma
图 2 两组患者肝移植术后Foxp3+调节性T细胞的表达变化
A图为肿瘤复发组，B图为肿瘤未复发组
Figure 2. The changes of Foxp3+Treg of patients in two groups after liver transplantation
表 1 肝癌肝移植患者的调节性T细胞与甲胎蛋白、效应性T细胞的关系
Table 1. The relationship between Treg and AFP, effective T cell of patients after liver transplantation for hepatocellular carcinoma
指标 APF CD3+T细胞 CD8+T细胞 r值 P值 r值 P值 r值 P值 术前Foxp3+Treg 0.52 0.010 -0.73 < 0.001 -0.78 < 0.001 术后Foxp3+Treg 0.53 0.014 -0.52 0.015 -0.56 0.009 
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