冷循环射频消融治疗后肝癌患者调节性T细胞变化及其对预后的影响

摘要

目的：探讨冷循环射频消融（RFA）治疗对肝癌（HCC）患者调节性T细胞（Treg）变化及其对预后的影响。方法流式细胞仪检测冷循环RFA治疗前，治疗后1、4、7和12个月后外周血Treg的变化。随访期间采用超声造影或肝脏增强CT评估疗效。采用受试者工作特征（ROC）曲线及Kaplan-Meier生存函数的方法分析Treg动态变化与肿瘤无进展生存期的关系。结果 RFA术后1个月，30例患者肿瘤缓解（TR）率93.3%（28/30），肿瘤进展（TP）率6.67%（2/30）。 RFA术前Treg（9.42±1.16）%，术后1个月（6.55±0.97）%，较术前显著下降（t=15.325，P＜0.01）。经12个月随访，TR率33.3%（10/30），TP率66.7%（20/30）。 TR组术前Treg为（8.75±0.72）%，显著低于TP组（9.76±1.20）%（t=-2.448，P=0.021）。 ROC曲线表明Treg谷值以4.82%为最佳临界值时，灵敏度为90.0%，特异度为60.0%；Treg达谷时间以5.5个月为最佳临界值，灵敏度为70.0%，特异度为85.0%。采用Kaplan-Meier曲线分析表明，肝癌RFA术后Treg谷值≤4.82%的肿瘤无进展生存率优于Treg谷值＞4.82%的患者；Treg达谷时间≥5.5个月的患者预后优于Treg达谷时间＜5.5个月的患者，Log-rank检验分别为字2=5.207，P =0.023；字2=22.079， P ＜0.01。结论冷循环RFA可以下调Treg水平，并且Treg谷值及Treg达谷时间在一定程度上反映RFA治疗HCC患者的预后。%Objective To investigate the changes of regulatory T cells (Treg) in patients with hepatocellular carcinoma (HCC) after ultrasound- guided percutaneous cool- tip radiofrequency ablation (RFA), and to discuss its influence on the prognosis. Methods A total of 30 patients with HCC were enrolled in this study. The percentage of Treg in peripheral blood was estimated with flow cytometry before RFA and one, 4, 7 and 12 months after RFA. During the follow-up period, the therapeutic effects were evaluated by contrast enhanced sonography or contrast enhanced CT scanning. By using the methods of receiver operating characteristic (ROC) curve and Kaplan-Meier survival function, the correlation of Treg dynamic changes with the progression-free survival time was analyzed. Results One month after RTA, the tumor response (TR) rate in the 30 patients was 93.3% (28/30), the tumor progression (TP) rate was 6.67%(2/30). The percentage of Treg before RFA was (9.42 ± 1.16)%, which decreased to (6.55 ± 0.97)% one month after RFA, the difference was statistically significant (t = 15.325, P <0.001). Twelve months after RFA, TR rate became 33.3%(10/30), and TP rate became 66.7%(20/30). The preoperative percentage of Treg of TR group was (8.75 ± 0.72)%, which was significantly lower than that of TP group (9.76 ± 1.20)%, the difference was statistically significant (t=-2.448, P=0.021). ROC curves indicated that the optimal cut-off value of Treg nadir was 4.82%, the sensitivity was 90.0% and the specificity was 60.0%. The optimal cut-off time to reach Treg nadir was 5.5 months, the sensitivity was 70.0% and the specificity was 85.0%. Kaplan-Meier curve analysis showed that after RFA the progression-free survival rate (PFS) of patients with Treg nadir ≤ 4.82% was significantly higher than that of patients with Treg nadir>4.82%. PFS of patients with reaching Treg nadir≥5.5 months was significantly higher than that of patients with reaching Treg nadir<5.5 months. Log-rank test results were字2=5.207, P=0.023; 字2=22.079, P < 0.001, respectively. Conclusion Percutaneous cool-tip radiofrequency ablation can decrease the percentage of Treg cells. Besides, Treg nadir and the time reaching Treg nadir can reflect the prognosis of HCC patients after RFA to a certain extent.