CDA C435T基因多态性显著延长吉西他滨治疗晚期非小细胞肺癌远期疗效  

CDA C435T gene polymorphism significantly extends the long-term efficacy of gemcitabine in advanced non-small cell lung cancer

作　　者：王梦娇 高超 王涛 张倩 文娟 吕冬梅 胡丽丽 WANG Mengjiao;GAO Chao;WANG Tao;ZHANG Qian;WEN Juan;LV Dongmei;HU Lili(School of Pharmacy,Xuzhou Medical University,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221000,Jiangsu,China;Department of Pharmacy,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221000,Jiangsu,China;Department of Oncology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221000,Jiangsu,China;Department of Medical records Room,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221000,Jiangsu,China)

机构地区：[1]徐州医科大学药学院,江苏徐州221000 [2]徐州医科大学附属医院药学部,江苏徐州221000 [3]徐州医科大学附属医院肿瘤内科,江苏徐州221000 [4]徐州医科大学附属医院病案室,江苏徐州221000

出　　处：《中国临床药理学与治疗学》2024年第12期1337-1343,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：江苏省卫健委2023年度药品临床综合评价项目(WJ20221507);徐州市科技局重点研发计划-面上项目(KC22263);江苏省药学会恒瑞医院药学基金项目(202041);江苏省研究型医院协会精益化用药基金项目(JY202033)。

摘　　要：目的:探讨胞苷脱氨酶(cytidine deaminase,CDA)C435T基因多态性对吉西他滨治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)远期疗效的影响。方法:收集2016年8月至2019年2月徐州医科大学附属医院接受吉西他滨-铂类治疗的非小细胞肺癌病例145例,记录年龄、性别、病理类型、临床分期(Ⅰ-ⅢA/ⅢB-Ⅳ)等基本临床特征,依据RECIST1.1标准评估,无病生存期(DFS)、无进展生存期(PFS)及总生存期(OS)为主要终点。检测CDA C435T基因型,病例分为野生型CC组与突变型CT/TT组。采用Kaplan-Meier法和log-rank检验分析CDA C435T与DFS、PFS及OS的关系,Cox模型分析预后影响因素。结果:Ⅰ-ⅢA期CC较CT/TT中位DFS延迟趋势不明显(16.8个月vs.35.7个月,P=0.294),中位OS无差异(54.3个月vs.81.9个月,P=0.256)。ⅢB-Ⅳ期CT/TT比CC中位PFS延长(10.4个月vs.5.0个月,P=0.009),中位OS无差异(16.2个月vs.24.3个月,P=0.087)。CC和CT/TT总体中位OS无差异(21.5个月vs.25.3个月,P=0.077)。Cox回归模型显示,CDA C435T是ⅢB-Ⅳ期PFS的独立影响因素(P=0.019)。结论:CDA C435T基因多态性对吉西他滨治疗ⅢB-Ⅳ期NSCLC的PFS具有预测性,CT/TT型明显延长。AIM:To research the effects of cytidine deaminase(CDA)C435T polymorphism on the long-term effectiveness of gemcitabine in nonsmall cell lung cancer(NSCLC).METHODS:Enrolled 145 NSCLC patients received gemcitabine-platinum regiments at the Affiliated Hospital of Xuzhou Medical University from August 2016 to February 2019,characteristics recorded such as:age,gender,pathological type,clinical stage(I-IIIA/IIIB-IV)and so on.Followed-up and evaluated according to RECIST1.1,the disease-free survival(DFS),progression-free survival(PFS)and overall survival(OS)was study endpoint.Cases were categorized into wild-type CC and mutant CT/TT group.Kaplan-Meier method and log-rank test were utilized to analyze the relationship between CDA C435T and DFS/PFS/OS.A cox model was implemented to analyze the prognostic factors.RESULTS:In stage I-IIIA,median DFS of CT/TT compared with CC was not obvious(16.8 vs.35.7 months,P=0.294),same in median OS(54.3 vs.81.9 months,P=0.256).In stage IIIB-IV,the median PFS in CT/TT was longer than CC(10.4 vs.5.0 months,P=0.009),the median OS was undifferentiated(16.2 vs.24.3 months,P=0.087).No difference of overall median OS in CC and CT/TT genotypes was seen(21.5 months vs.25.3 months,P=0.077).Cox regression model showed CDA C435T polymorphism was an independent factor of PFS in stage IIIB-IV(P=0.019).CONCLUSION:CDA C435T polymorphism shows a function as a prediction influencing PFS of gemcitabine in IIIB-IV NSCLC,CT/TT genotype is significantly prolonged.

关 键 词：CDA C435T基因 非小细胞肺癌 化疗 多态性 预后 

分 类 号：R968[医药卫生—药理学]