前列腺癌组织中雄激素受体剪接变异体7的表达对转移性前列腺癌患者总生存的影响  

Impact of AR-V7 expression on overall survival for patients with metastatic prostate cancer

作　　者：瞿元元[1] 叶定伟[1] 戴波[1] 孔蕴毅[2] 常坤[1] 顾成元[1] 孙自捷 张海梁[1] 朱耀[1] 

机构地区：[1]复旦大学附属肿瘤医院泌尿外科复旦大学上海医学院肿瘤学系,上海200032 [2]复旦大学附属肿瘤医院泌尿外科复旦大学上海医学院病理科,上海200032 [3]美国斯坦福大学医学院泌尿外科美国斯坦福大学医学院遗传学系

出　　处：《中华外科杂志》2014年第8期622-626,共5页Chinese Journal of Surgery

基　　金：上海市科委医学引导项目（124119a7300）;上海市科委＂创新行动计划＂国际学术合作交流项目（12410709300）;上海市卫生系统优秀青年人才培养计划项目（XYQ2013102）

摘　　要：目的 探讨前列腺癌组织中雄激素受体剪接变异体7（AR-V7）的表达对转移性前列腺癌患者总生存的影响.方法 选取2002年1月至2010年6月经病理诊断确诊为前列腺腺癌的1 13例患者为研究对象.回顾性收集所有患者的临床病理资料,包括确诊时年龄、确诊时血清前列腺特异性抗原（PSA）值、确诊时Gleason评分、确诊时M分期,内分泌治疗过程中PSA最低值、到达PSA最低值时间,生存状态,死亡患者的生存时间和死亡原因.利用免疫组化技术检测前列腺癌原发灶中AR-V7的表达.利用t检验或Х^2检验分析前列腺癌组织中AR-V7的表达与患者临床病理特征的相关性.运用Cox比例风险模型分析AR-V7的表达及患者临床病理特征对总生存的影响.结果 内分泌治疗过程中血清PSA最低值为0- 143.0 μg/L,中位值0.7μg/L.到达PSA最低值时间为0.9 -71.0个月,中位时间8.1个月.至随访截止日期2014年3月12日,113例患者中67例（59.3％）死亡,生存时间5- 135个月,中位生存时间96个月.前列腺癌组织中AR-V7的阳性表达率为20.4％（23/113）.前列腺癌组织中表达AR-V7的患者确诊时血清PSA值显著低于不表达AR-V7的患者（t=2.521,P=0.013）.Cox多因素分析结果表明,AR-V7的表达（HR=2.421,P=0.002）和内分泌治疗过程中到达PSA最低值时间（HR=1.019,P=0.022）为转移性前列腺癌患者总生存的独立预后因素.结论 前列腺癌组织中AR-V7的表达和内分泌治疗过程中达到PSA最低值时间为转移性前列腺癌患者总生存的独立预后因素.针对AR-V7的治疗有望改善转移性前列腺癌患者的预后.Objective To investigate the impact of androgen receptor splice variant 7 （AR-V7） expression on overall survival for patients with metastatic prostate cancer.Methods The data of 113 diagnosed metastatic prostate cancer patients from January 2002 to June 2010 were collected retrospectively,including patient＇s age at diagnosis,prostate-specific antigen （PSA） level at diagnosis,Gleason score,clinical stage,PSA nadir during hormonal therapy,the time to PSA nadir,vital status,survival time and cause of death.The expression of AR-V7 in prostate cancer tissue was detected by using immunohistochemical staining.The correlation of AR-V7 expression and patient clinicopathological characteristics in all patients were analysed using Student t-test or Chi-square test.Cox proportional hazards regression models were used to evaluate the predictive role of AR-V7 expression and patient characteristics for overall survival.Results The median PSA nadir was 0.7 μg/L （ranged from 0.0 to 143.0 μg/L）.The median time to PSA nadir was 8.1 months （ranged from 0.9 to 71.0 months）.The follow-up was performed until March 12,2014.During the follow-up period,67 of 113 metastatic prostate cancer patients （59.3％） died and the median overall survival was 96 months （ranged from 5 to 135 months）.The AR-V7 detection rate was 20.4％ （23/113）.The serum PSA level in patients with positively expression of AR-V7 was significantly higher than that without AR-V7 expression （t =2.521,P =0.013）.Multivariate Cox regression analysis indicated that the expression of AR-V7 （HR =2.421,P =0.002） and time to PSA nadir （HR =1.019,P =0.022） were independent prognostic factors of overall survival for metastatic prostate cancer patients.Conclusions The expression of AR-V7 in prostate cancer tissues and time to PSA nadir during hormonal therapy are independent prognostic factors of overall survival for metastatic prostate cancer patients.Therapy targeting AR-V7 may improve prognosis of metastatic prostate cancer patients.

关 键 词：前列腺肿瘤 肿瘤转移 雄激素受体 预后 

分 类 号：R737.25[医药卫生—肿瘤]