TS基因3′-UTR多态性与晚期肺腺癌患者对培美曲塞敏感度的关系

 目的
探讨胸苷酸合成酶(thymidylate synthase，TS）基因3′端非翻译区(untranslated region，UTR)1 494 bp处6 bp缺失或插入多态(-6 bp或+6 bp)与晚期肺腺癌患者接受培美曲塞方案化疗敏感度的关系。方法采用AollgTM探针结合实时荧光PCR技术检测接受培美曲塞方案化疗的106例晚期肺腺癌患者外周血中TS基因型，分析携带TS不同基因型患者与化疗敏感度的关系。结果（1）106例晚期肺腺癌患者中TS基因3′- UTR 1 494 bp处6 bp缺失或插入多态基因频率分别为:-6 bp/-6 bp 557%（59/106），-6 bp/+6 bp 44.3%（47/106），+6 bp/+6 bp 0（0/106）；（2）总体近期有效率(CR + PR)为23.58%，携带TS基因3′-UTR 1494 bp处-6 bp/- 6 bp基因型化疗有效率是携带-6 bp/+6 bp基因型有效率的4.382倍 (95% CI:1.462～13.130，P=0.008)；（3）携带-6 bp/-6 bp基因型与携带-6 bp/+6 bp基因型患者的中位PFS、中位OS差异均具有统计学意义（3.400月vs.2.477月，P=0001；14.239月vs.12.194月，P=0.000）；提示携带-6 bp/-6 bp基因型患者在PFS、OS具有显著优势。（4）Cox多因素分析临床病理因素与生存时间的关系得出年龄越大，病理分期越晚，携带TS3′- UTR 1 494位点处-6 bp/+6 bp基因型患者的死亡风险越大。结论TS基因3′- UTR 1 494 bp处6 bp缺失或插入多态(-6 bp或+6 bp)可能与晚期肺腺癌患者培美曲塞方案化疗敏感度相关，可作为晚期肺腺癌患者个体化治疗预测因子之一。

Polymorphism in 3′-untranslated Region of Thymidylate Synthase Gene and Sensitivity of Advanced Lung Adenocarcinoma to Pemetrexed

Objective
This study was to investigate the relationship between Polymorphism missing or insertion in the 3′-untranslated region of thymidylate synthase gene and the sensitivity to the pemetrexed therapy for advanced lung adenocarcinoma.MethodsThe AollgTM probe combined with real-time fluorescence PCR technology was used to test 106 patients’ with lung adenocarcinoma accepted pemetrexed therapy on their genotype TS of peripheral blood. We analyzed the patients carrying different genotypes of TS for the relationship between TS and chemotherapic sensitivity.Results(1)Among the 106 cases of patients with advanced lung adenocarcinoma， the frequency of polymorphism gene 6bp missing or insertion in the TS gene 3′-UTR 1494 bp were respectively: -6 bp/-6 bp 55.7%（59/106），-6 bp/+6 bp 44.3%（47/106），+6 bp/+6 bp 0%（0/106）. (2)The overall recent response rate was 23.58%. The chemotherapy on patients with -6 bp/-6 bp genotype was 4.382 times as effective as the ones with the -6 bp/+6 bp genotype ( 95% CI，1.462～13.130，P=0.008)；(3) The median PFS and the median OS difference had statistical significance between patients with the -6 bp /-6 bp genotype and those with the -6 bp / + 6 bp genotypes（3.400 months vs. 2.477 months，P=0.001；14.239 months vs. 12.194 months，P=0.000）， suggesting that the patients with the -6 bp /-6 bp genotypes had significant advantage in both OS， PFS. (4) Cox regression analysis showed the relation between patients’ age and the pathologic stage: elder patients with -6 bp/+6 bp genotype were faced with higher risk of death.Conclusion6 bp polymorphism gene’ missing or insertion in the TS might influence the sensitivity to the pemetrexed therapy for advanced lung adenocarcinoma， which could be used as one of the prognositic genes for personalized treatment.