Dong Honglin, Bao Dengke, Guo Xu, Hu Jie, Li Xiaofei, Wan Shaogui, Xing Jinliang
Department of Vascular Surgery, Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
Tumour Biol. 2015 Sep;36(9):7151-7. doi: 10.1007/s13277-015-3447-6. Epub 2015 Apr 16.
Genetic polymorphisms of thymidylate synthase (TYMS) gene have been reported to be associated with development or prognosis of several cancers. However, the association between polymorphisms of TYMS gene and clinical outcomes of non-small cell lung cancer (NSCLC) patients are still unknown. In the present study, we investigated the associations between single nucleotide polymorphisms (SNPs) of TYMS gene and response to chemotherapy as well as clinical outcomes in NSCLC patients. Five SNPs in TYMS gene were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 500 NSCLC patients, and their associations with NSCLC outcomes were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant, and recessive models). Our data showed that there was no significant association between individual SNP and overall survival of NSCLC patients. However, SNP rs2847153 was significantly associated with NSCLC recurrence under recessive model. We further identified a significant interaction between rs2847153 and chemotherapy in modifying clinical outcome of patients. Our data showed that individuals carrying GG/GA genotypes of rs2847153 had a significantly better response to chemotherapy when comparing to those carrying AA genotype. Conclusively, our data suggest that SNPs rs2847153 in TYMS gene may be a potential biomarker for predicting clinical outcome and personalized treatment in NSCLC patients.
据报道，胸苷酸合成酶（TYMS）基因的遗传多态性与多种癌症的发生发展或预后相关。然而，TYMS基因多态性与非小细胞肺癌（NSCLC）患者临床结局之间的关联仍不清楚。在本研究中，我们调查了TYMS基因单核苷酸多态性（SNP）与NSCLC患者化疗反应及临床结局之间的关联。使用Sequenom iPLEX基因分型系统对500例NSCLC患者的医院队列中的TYMS基因5个SNP进行基因分型，并在三种遗传模型（加性、显性和隐性模型）下通过Cox比例风险回归分析评估它们与NSCLC结局的关联。我们的数据表明，单个SNP与NSCLC患者的总生存期之间无显著关联。然而，在隐性模型下，SNP rs2847153与NSCLC复发显著相关。我们进一步确定了rs2847153与化疗在改变患者临床结局方面存在显著相互作用。我们的数据表明，与携带AA基因型的个体相比，携带rs2847153的GG/GA基因型的个体对化疗反应显著更好。总之，我们的数据表明，TYMS基因中的SNP rs2847153可能是预测NSCLC患者临床结局和个体化治疗的潜在生物标志物。
