登录    
  
首页 > 期刊论文 > 论文摘要
胸苷酸合酶基因变数串联重复多态性与培美曲塞治疗晚期非小细胞肺癌疗效相关性分析
         
Association between variable number of tandem repeat polymorphism of thymidylate synthase gene and efficacy of pemetrexed in the treatment of advanced non-small cell lung cancer

摘    要
目的:探讨胸苷酸合酶(thymidylate synthase,TS)基因5'-端非编码区(5'-untranslation region,5'-UTR)变数串联重复(variable number of tandem repeat,VNTR)多态性与培美曲塞治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)疗效的相关性。方法:回顾性分析90例晚期NSCLC患者的临床参数;抽取患者外周血标本并提取DNA,通过复合扩增荧短片段重复序列聚合酶链反应(short tandem repeat-polymerase chain reaction,STR-PCR)结合毛细血管电泳的方法检测TS基因5'-UTR VNTR的多态性。结果:TS基因5'-UTR VNTR纯合状态(2R/2R+3R/3R)与杂合状态(2R/3R+3R/4R)均与培美曲塞的临床疗效无相关性,其无进展生存期分别为112 d和94 d(P=0.549),疾病控制率为64.3%和67.6%(P=0.745),客观缓解率为12.5%和8.8%(P=0.591);2R多态性(2R/2R+2R/3R)和3R多态性(3R/3R+3R/4R)亦与培美曲塞的临床疗效无相关性(无进展生存期:P=0.518,疾病控制率:P=0.631,客观缓解率:P=0.541)。结论:TS基因5'-UTR VNTR多态性与培美曲塞治疗NSCLC疗效可能无相关性。
标    签 癌,非小细胞肺   胸苷酸合酶   抗肿瘤联合化疗方案   多态性,限制性片段长度   Carcinoma, non-small cell lung   Thymidylate synthase   Antineoplastic combined chemotherapy protocols   Polymorphism, restriction fragment length  
 
Abstract
Objective: To investigate the association between variable number of tandem repeat(VNTR) polymorphism in 5'-untranslation region(5'-UTR) of thymidylate synthase(TS) gene and the efficacy of pemetrexed-based treatment in non-small cell lung cancer(NSCLC). Methods: Peripheral blood samples were collected from 90 patients with advanced NSCLC and the genomic DNAs were extracted from these blood samples. The VNTR polymorphism in 5'-UTR of TS gene was detected by fluorescent labeled PCR and multiplex short tandem repeat polymerase chain reaction in combination with capillary electrophoresis. Results: The homozygosis(3R/3R and 2R/2R) and heterozygosis(2R/3R and 3R/4R) of VNTR polymorphism in 5'-UTR of TS gene were not associated with the efficacy of pemetrexed. The progression-free survivals, disease control rates and the objective response rates in patients harboring homozygosis(3R/3R and 2R/2R) and heterozygosis(2R/3R and 3R/4R) were 112 and 94 d(P=0.549), 64.3% and 67.6%(P=0.745), and 12.5% and 8.8%(P=0.591), respectively. The patients harboring 2R alleles had similar clinical outcomes as compared with those harboring 3R alleles(progression-free survival:P=0.518; disease control rate:P=0.631; objective response rate:P=0.541). Conclusion: TS gene VNTR polymorphism may not be associated with clinical outcomes of advanced NSCLC treated with pemetrexed.

中图分类号 R734.2   DOI 10.3781/j.issn.1000-7431.2012.07.011

 
  购买该论文  中国光学期刊网论文下载说明
      


所属栏目 临床研究

基金项目

收稿日期 2012/1/26

修改稿日期 2012/6/8

网络出版日期

作者单位点击查看


引用该论文: HU Qiong,LI Xue-fei,REN Sheng-xiang,CHEN Xiao-xia,TANG Liang,ZHANG Jie,ZHOU Cai-cun. Association between variable number of tandem repeat polymorphism of thymidylate synthase gene and efficacy of pemetrexed in the treatment of advanced non-small cell lung cancer[J]. Tumor, 2012, 32(7): 539~545
胡琼,李雪飞,任胜祥,陈晓霞,唐亮,张劼,周彩存. 胸苷酸合酶基因变数串联重复多态性与培美曲塞治疗晚期非小细胞肺癌疗效相关性分析[J]. 肿瘤, 2012, 32(7): 539~545


论文评价
共有人对该论文发表了看法,其中:
人认为该论文很差
人认为该论文较差
人认为该论文一般
人认为该论文较好
人认为该论文很好
分享论文
分享到新浪微博 分享到腾讯微博 分享到人人网 分享到 Google Reader 分享到百度搜藏分享到Twitter

参考文献
【1】SØRENSEN J B. Pharmacokinetic evaluation of pemetrexed[J]. Expert Opin Drug Metab Toxicol, 2011, 7(7):919-928.
 
【2】SCAGLIOTTI G V, PARIKH P, VON PAWEL J, et al. PhaseⅢ study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer[J]. J Clin Oncol, 2008, 26(21):3543-3551.
 
【3】HANNA N, SHEPHERD F A, FOSSELLA F V, et al. Randomized phase Ⅲ trial of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy[J]. J Clin Oncol, 2004, 22(9):1589-1597.
 
【4】CIULEANU T, BRODOWICZ T, ZIELINSKI C, et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small cell lung cancer:a randomised, double-blind, phase 3 study[J]. Lancet, 2009, 374(9699):1432-1440.
 
【5】ETTINGER D S, AKERLEY W, BORGHAEI H, et al. NCCN clinical practice guideline in oncology version 2.2012[EB/OL].www.nccn.com. 2011-10-04.
 
【6】KAIRA K, OHDE Y, NAKAGAWA K, et al. Thymidylate synthase expression is closely associated with outcome in patients with pulmonary adenocarcinoma[J/OL]. Med Oncol, 2011-09-24.
 
【7】TANAKA F, WADA H, FUKUI Y, et al. Thymidylate synthase (TS) gene expression in primary lung cancer patients:a large-scale study in Japanese population[J]. Ann Oncol, 2011, 22(8):1791-1797.
 
【8】TAKEZAWA K, OKAMOTO I, OKAMOTO W, et al. Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer[J]. Br J Cancer, 2011, 104(10):1594-1601.
 
【9】KAWAKAMI K, WATANABE G. Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene[J]. Cancer Res, 2003, 63(18):6004-6007.
 
【10】PARK D J, STOEHLMACHER J, ZHANG W, et al. Thymidylate synthase gene polymorphism predicts response to capecitabine in advanced colorectal cancer[J]. Int J Colorectal Dis, 2002, 17(1):46-49.
 
【11】OTT K, VOGELSANG H, MARTON N, et al. The thymidylate synthase tandem repeat promoter polymorphism:A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer[J]. Int J Cancer, 2006, 119(12):2885-2894.
 
【12】OZASA H, OGURI T, UEMURA T, et al. Significance of thymidylate synthase for resistance to pemetrexed in lung cancer[J]. Cancer Sci, 2010, 101(1):161-166.
 
【13】CEPPI P, RAPA I, LO IACONO M, et al. Expression and pharmacological inhibition of thymidylate synthase and Src kinase in non-small cell lung cancer[J]. Int J Cancer, 2012, 130(8):1777-1786.
 
【14】TAKEDA M, OKAMOTO I, HIRABAYASHI N, et al. Thymidylate synthase and dihydropyrimidine dehydrogenase expression levels are associated with response to S-1 plus carboplatin in advanced non-small cell lung cancer[J]. Lung Cancer, 2011, 73(1):103-109.
 
【15】KORNMANN M, HEBART H, DANENBERG K, et al. Response prediction in metastasised colorectal cancer using intratumoural thymidylate synthase:Results of a randomised multicentre trial[J/OL]. Eur J Cancer, 2011-11-29.
 
【16】ISHIDA Y, KAWAKAMI K, TANAKA Y, et al. Association of thymidylate synthase gene polymorphism with its mRNA and protein expression and with prognosis in gastric cancer[J]. Anticancer Res, 2002, 22(5):2805-2809.
 
【17】BRABENDER J, METZGER R, VALLB?HMER D, et al. Roles of thymidylate synthase and dihydropyrimidine dehydrogenase expression in blood as predictors of response to multimodal therapy in esophageal cancer[J]. Surgery, 2012, 151(2):306-312.
 
【18】SOBIN L H, GOSPODAROWICZ M K, WITTEKIND C H, eds. International Union Against Cancer (UICC) TNM Classification of Malignant Tumours, 7th Edition[M]. United Kingdom, Oxford:Wiley-Blackwell Publ Corp, 2009:1-256.
 
【19】EDGESB, BYRDDR, CARDUCCIMA, et al. American Joint Committee on Cancer (AJCC) Cancer Staging Handbook. 7th Edition[M]. NewYork:Springer-Verlag Publ Corp, 2009:1-195.
 
【20】MANDOLA M V, STOEHLMACHER J, MULLER-WEEKS S, et al. A novel single nucleotide polymorphism within the 5' tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity[J]. Cancer Res, 2003, 63(11):2898-2904.
 
【21】GORLICK R, METZGER R, DANENBERG K D, et al. Higher levels of thymidylate synthase gene expression are in pulmonary as compared with hepatic metastases of colorectal adenocarcinoma[J]. J Clin Oncol, 1998, 16(4):1465-1469.
 
【22】GIOVANNETTI E, BACKUS HH, WOUTERS D, et al. Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels[J]. Br J Cancer, 2007, 96(5):769-775.
 
【23】LU J W, GAO C M, WU J Z, et al. Polymorphism in the 3'-untranslated region of the thymidylate synthase gene and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy[J]. J Hum Genet, 2006, 51(3):155-160.
 
【24】吴玉玉, 黄朝晖, 华东. 胸苷酸合成酶基因多态对接受氟尿嘧啶辅助化疗胃癌患者预后的影响[J]. 肿瘤, 2008, 28(12):1086-1089.
 
相关信息
   标题 相关频次
 表皮生长因子受体基因CA简单重复序列多态性与晚期小细胞肺癌患者表皮生长因子受体酪氨酸激酶抑制剂临床疗效间的关系
 10
 培美曲塞治疗非小细胞肺癌无症状脑转移临床分析
 8
 人肺腺癌细胞株A549和A549/DDP的比较蛋白质组学研究
 8
 人肺腺癌吉非替尼耐药细胞株中微小RNA的表达谱
 7
 非小细胞肺癌患者EGFR基因突变状态影响因素的临床分析
 6
 扩增阻滞突变系统法检测非小细胞肺癌微小标本表皮生长因子受体突变
 6
 西妥昔单抗联合多西紫杉醇对EGFR-TKI获得性耐药的非小细胞肺癌细胞的作用
 6
 化疗序贯厄洛替尼治疗二线厄洛替尼耐药晚期非小细胞肺癌的临床疗效和安全性
 5
 硫酸基转移酶1E1基因单核苷酸多态性联合吸烟与肺癌易感性的关系
 5
 血管内皮生长因子C过表达或抑制表达对人小细胞肺癌NCI-H446细胞生物学行为的影响
 5
 GRIM-19基因对肺腺癌耐药细胞株A549/DDP药物敏感性及相关基因表达的影响
 4
 ⅠB期非小细胞肺癌中K-ras的表达对辅助化疗预后的影响
 4
 cRGD-氧化铁纳米粒的构建及应用于核磁共振成像诊断中的动物研究
 4
 DNA修复基因MMS19单核苷酸多态性与非小细胞肺癌组织学类型的关系
 4
 H2O2氧化刺激对紫杉醇耐药和敏感肺癌细胞的不同影响
 4
 KDR基因重组的T7噬菌体疫苗构建及其对小鼠Lewis肺癌抑制作用的研究
 4
 Luffin-β靶向融合免疫毒素的构建、表达及对非小细胞肺癌的抑制作用
 4
 靶向血管新生肽修饰的氧化铁纳米粒对荷瘤裸鼠磁热疗的研究
 4
 初治晚期无症状脑转移非小细胞肺癌患者全脑放疗的时序探讨
 4
 单药培美曲塞二线治疗晚期非小细胞肺癌的疗效观察
 4
 厄洛替尼治疗晚期非小细胞肺癌的临床研究
 4
 非小细胞肺癌组织中血管内皮生长因子表达与树突状细胞分布的关系
 4
 高海拔地区老年非小细胞肺癌患者接受全电视胸腔镜下肺叶切除的安全性和预后分析
 4
 甲状腺癌的分子靶向治疗进展
 4
 老年晚期非小细胞肺癌治疗进展
 4
 上皮-间质转化和胰岛素样生长因子Ⅰ型受体在非小细胞肺癌EGFR-TKIs获得性耐药中的作用
 4
 首剂负荷量伊班膦酸钠治疗肺癌转移性骨痛的疗效和安全性分析
 4
 托瑞米芬联合长春瑞滨和顺铂二线治疗中晚期非小细胞肺癌的疗效
 4
 微RNA-21与BIM蛋白在逆转肺腺癌细胞对EGFR-TKIs耐药中的相互拮抗作用
 4
 盐酸厄洛替尼所致皮疹的免疫机制研究
 4

  热点专题


关于我们  |   联系我们  |   广告投放  |   《肿瘤》杂志社版权所有 《肿瘤》杂志社   © 中国 上海 2014.3
沪ICP备15036656号-2