膀胱肿瘤基因多态性指导灌注药物选择分析  

Guiding Intravesical Chemotherapy by Genetic Polymorphisms Analysis in Bladder Cancer Patients

作　　者：何雪峰[1] 欧阳骏[1] 李耀军[1] 

机构地区：[1]苏州大学附属第一医院泌尿外科,苏州215006

出　　处：《航空航天医学杂志》2014年第10期1369-1372,共4页Journal of Aerospace medicine

摘　　要：目的：检测谷胱甘肽S转移酶P1（Glutathione S－transferase P1，GSTP1）、多药耐药基因1（Multidrug－re-sistance Gene 1，MDR1）、醌氧化还原酶（NADPH quinone oxido－reductase，NQO1）基因多态性，评估非肌层浸润性膀胱癌（ non muscle－invasive bladder cancer ， NMIBC）患者对膀胱灌注化疗药物表阿霉素和丝裂霉素 C的敏感性。方法选取112例2011年10月-2013年10月行TUR－Bt术确诊的初发NMIBC患者，应用聚合酶链反应－直接碱基序列分析基因分型技术（sequence based genotyping ， PCR－SBT）法检测患者外周血中GSTP1、MDR1、NQO1基因多态性，预测患者对表阿霉素和丝裂霉素 C的敏感性，选择敏感性高的药物作为膀胱灌注药物，随访观察患者术后复发情况，分析GSTP1、MDR1、NQO1基因多态性检测对NMIBC患者膀胱灌注化疗药物选择的意义。结果12例MNIBC患者，随访时间6-24个月，平均随访20.5±2.7月，复发17例，复发率15.18％；表阿霉素膀胱灌注52例，丝裂霉素C灌注60例；以敏感性药物膀胱灌注的患者48例，表阿霉素和丝裂霉素C各24例，随访期间复发6例，复发率为12.5％；按经验选择中度敏感性药物进行膀胱灌注患者64例，表阿霉素及丝裂霉素C分别为28例、36例，随访期间出现11例复发，复发率为17.19％，两者差异有统计学意义（P＜0.05）。结论 NMIBC 患者膀胱灌注化疗前通过检测GSTP1、MDR1、NQO1基因多态性预测患者对表阿霉素和丝裂霉素 C的敏感性，选择敏感性药物化疗，能有效降低NMIBC复发率，此方法对NMIBC术后化疗药物的选择具有指导性意义。Objective To detect Glutathione S transferase P1 （GSTP1）, multidrug-resistance gene 1（MDR1） and NADPH quinone oxidoreductase1（NQO1）, in the evaluation of the sensitivity of patients presenting with non -muscle invasive bladder cancer （ NMIBC） to epirubicin and mitomycin C.Methods Between October 2011 and October 2013 , we enrolled 112 early NMIBC patients diagnosed by TUR -Bt surgery.Polymerase chain reaction -sequence based geno-typing （PCR-SBT） enabled detection of GSTP1, MDR1, and NQO1 gene polymorphisms to predict patient sensitivity to epirubicin and mitomycin C , and to select the most sensitive drug as the intravesical drug.By following patients and observing their post -operative recurrence , we analyzed the possibility of selecting intravesical chemotherapy for NMIBC by detecting gene polymorphisms in GSTP 1, MDR1, and NQO1.Results Patients were followed -up for 6 -24 months, with an average follow -up of 20.5 ±2.7 months.Recurrence was found in 17 cases （15.18%）.Among 52 patients treated with intravesical epirubicin and 60 patients treated with mitomycin C , 24 cases were sensitive to epirubi-cin and 24 to mitomycin C.Six cases （12.5%） showed recurrence during follow -up.64 patients were treated with mod-erately sensitive drugs by empiricism , including 28 cases of intravesical epirubicin and 36 cases of mitomycin C.Eleven cases （17.19%） showed recurrence during follow -up.Recurrence rates between sensitive and moderately sensitive drugs was significant （P〈0.05）.Conclusions Detection of GSTP1, MDR1, NQO1 gene polymorphisms in NMIBC pa-tients prior to intravesical chemotherapy predicts sensitivity to epirubicin and mitomycin C , and permits selection of a sensitive agent to reduce NMIBC recurrence.

关 键 词：非肌层浸润性膀胱癌 表阿霉素 丝裂霉素C 膀胱灌注 聚合酶链反应直接测序 

分 类 号：R730.41[医药卫生—肿瘤]