Hu Qiong, Li Xuefei, Su Chunxia, Chen Xiaoxia, Gao Guanghui, Zhang Jie, Zhao Yinmin, Li Jiayu, Zhou Caicun
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine;
Exp Ther Med. 2012 Dec;4(6):1010-1016. doi: 10.3892/etm.2012.730. Epub 2012 Sep 28.
One of the target genes of pemetrexed (PEM), thymidylate synthase (TS), has been shown to have a close association with its efficacy. TS gene polymorphisms have been shown to be associated with the efficacy of antifolate treatment in enteron tumors. The purpose of this study was to investigate the clinical significance of TS gene polymorphisms in patients with advanced NSCLC receiving PEM-based treatment. The variable nucleoid tandem repeat in the 5'-UTR region was amplified and detected using fluorescently labeled multiplex short tandem repeat polymerase chain reaction. The polymorphism in the 3'-UTR region of the TS gene was detected using the Taqman probe. Efficacy of PEM was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1. None of the genotypes were associated with gender, smoking status and age. Disease control rate (DCR), objective response rate (ORR) and progression-free survival (PFS) were similar between patients harboring 2R and 3R alleles (PFS, p=0.518; DCR, p=0.631; ORR, p=0.541), as well as those with a 6-bp insertion and 6-bp deletion (PFS, p=0.776; DCR, p=0.626; ORR, p=0.330). To study the combined effect of TS polymorphisms, the study population was divided into three groups: 2R&6 del, 2R&6 ins and 3R&6 del. No significant differences were observed among the different groups according to DCR (p=0.517), ORR (p=0.611) and PFS (p=0.938). In conclusion, polymorphisms of the TS gene do not appear to be a prognostic marker for advanced NSCLC patients receiving PEM-based treatment.
培美曲塞（PEM）的靶基因之一胸苷酸合成酶（TS）已被证明与其疗效密切相关。TS基因多态性已被证明与肠道肿瘤中抗叶酸治疗的疗效相关。本研究的目的是探讨TS基因多态性在接受基于PEM治疗的晚期非小细胞肺癌（NSCLC）患者中的临床意义。使用荧光标记的多重短串联重复聚合酶链反应扩增并检测5'-UTR区域中的可变核苷串联重复序列。使用Taqman探针检测TS基因3'-UTR区域中的多态性。根据实体瘤疗效评价标准1.1版评估PEM的疗效。所有基因型均与性别、吸烟状况和年龄无关。携带2R和3R等位基因的患者之间的疾病控制率（DCR）、客观缓解率（ORR）和无进展生存期（PFS）相似（PFS，p = 0.518；DCR，p = 0.631；ORR，p = 0.541），携带6-bp插入和6-bp缺失的患者之间也是如此（PFS，p = 0.776；DCR，p = 0.626；ORR，p = 0.330）。为了研究TS多态性的联合效应，将研究人群分为三组：2R&6 del、2R&6 ins和3R&6 del。根据DCR（p = 0.517）、ORR（p = 0.611）和PFS（p = 0.938），不同组之间未观察到显著差异。总之，TS基因多态性似乎不是接受基于PEM治疗的晚期NSCLC患者的预后标志物。
