氩氦刀冷冻消融治疗乙型肝炎病毒相关性肝细胞癌前后PD-1的变化及其与预后的关系

摘要

目的 观察氩氦冷冻消融治疗对乙型肝炎病毒相关性肝细胞癌(HCC)患者外周血细胞程序性死亡受体-1(PD-1)表达的影响,分析PD-1与HCC病程及患者预后的关系.方法 收集2006年1月-2009年1月收治的乙型肝炎病毒相关性HCC患者141例,其中男109例,女32例,年龄28～71岁,巴塞罗那分期(BCLC)早期46例,中期63例,进展期32例.采用流式细胞仪检测患者外周血细胞PD-1表达的百分比,分析PD-1与HCC进展的关系.对109例早、中期HCC患者进行氩氦冷冻消融治疗,比较治疗前后患者外周血PD-1表达的变化.将早期及中期患者根据术前PD-1表达的中位值(10.88%)分为4组,即早期低表达组(4.05%±1.28%,n=23)、中期低表达组(9.26%士1.63%,n=31)、早期高表达组(9.26%士3.09%,n=23)和中期高表达组(18.05%士3.78%,n=32),采用Kaplan-Meier法计算各组的无肿瘤生存时间(TFS)和总生存时间(OS)并进行比较.结果 PD-1表达水平在BCLC早期患者中为6.66%土3.52 %,中期患者中为13.72%士5.29%,进展期患者中为20.28%±11.89%.氩氦刀冷冻消融治疗后4周,109例HCC患者PD-1表达水平均较术前降低,其中11例术后复发患者复发后的PD-1表达较术后明显升高.PD-1高表达组(包括早期和中期)的TFS及OS均较低表达组(包括早期和中期)明显缩短.结论 HCC患者外周血细胞PD-1分子的表达随肿瘤进展而逐渐增加,氩氮刀冷冻消融治疗可降低HCC患者PD-1的表达；术前PD-1水平可用于预测HOC患者氩氦刀术后的生存期.%Objective To investigate the relationship of the expression of circulating programmed death-1 (PD-1) to the disease course of hepatocellular carcinoma (HCC), to explore the influence of cryoablation on the changes in PD-1 in peripheral blood, and to analyze the correlation between PD-1 and the prognosis of HCC patients. Methods The expression of circulating PD-1 was determined by flow cytometry to analyze the correlation between the expressions of PD-1 and progression of HCC. Of 141 patients with HCC, 109 underwent argon-helium cryoablation, the expressions of PD-1 in peripheral blood pre- and post-therapy were then detected and the changes were recorded thereafter. According to median percentage of PD-1 pre-cryoablation> 46 patients with early-stage HCC were assigned into tow-expression group (PD-1 4.05% ±1.28%, n=23) and high-expression group (9.26% ± 3.09%, n=23), and 63 patients with intermediate-stage HCC into low-expression group (9.26%±1. 63%, n=31) and high-expression group (18.05%±3. 78%, n=32). The tumor free survival (TFS) and overall survival (OS) were calculated and compared by using Kaplan-Meier Survival Analysis. Results The expression of circulating PD-1 were 6.66% ± 3. 52% in BCLC early-stage patients with HCC, 13. 72% ± 5.29% in intermediate-stage cases, and 20. 28%±11.89%% in advanced-stage cases. After cryoablation, the frequency of PD-1 expression decreased compared with that of pre-cryoablation. In 11 patients with tumor recurrence, the frequency of PD-1 expression rose prominently compared to that of post-cryoablatioa In both early- and intermediate-stage HCC patients, TFS and OS were shorter in patients with high expression of PD-1 compared with those with low expression of PD-1. Conclusions The expressions of circulating PD-1 increases with tumor progression. After argon-helium cryoablation, a reduction of PD-1 expression in HCC patients can be achieved. Increased expression of PD-1 may provide a reference for prediction of survival time in HCC patients after cryoablation.