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  

Changes in PD-1 and effect thereof on prognosis of patient after argon-helium cryoablation for hepatitis B related-hepatocellular carcinoma

作　　者：周霖[1] 曾珍[1] 石峰[2] 张敏娜[1] 陈艳[1] 常秀娟[1] 陆荫英[1] 白文林[1] 曲建慧[1] 王春平[1] 王宏[1] 楼敏[1] 王福生[2] 吕吉云[1] 杨永平[1] 

机构地区：[1]解放军302医院肝癌治疗研究中心,北京100039 [2]解放军302医院全军传染病研究所,北京100039

出　　处：《解放军医学杂志》2011年第10期1031-1036,共6页Medical Journal of Chinese People's Liberation Army

基　　金：国家科技重大专项课题(2008ZX10002-018);首都医学发展基金课题(2007-1021,2009-2041)

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%±1.63%,n=31)、早期高表达组(9.26%±3.09%,n=23)和中期高表达组(18.05%±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%±3.52%,中期患者中为13.72%±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,氩氦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HCC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 low-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-cryoablation.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.

关 键 词：程序性死亡受体-1 癌 肝细胞 冷冻外科手术 预后 

分 类 号：R735.705.45[医药卫生—肿瘤]