检测外周血相关基因预测培美曲塞治疗晚期非小细胞肺癌疗效的研究

Detect the related gene of TS and study on the prediction of the pemetrexed treatment in advanced non-small cell lung cancer

目的探讨培美曲塞治疗晚期非小细胞肺癌（NSCLC）的疗效及预后因子。方法回顾性分析2008年3月-2010年3月在河南省人民医院接受培美曲塞联合顺铂一线化疗的56例ⅢB、Ⅳ期NSCLC患者。采用荧光定量PCR方法检测患者外周血TS、DHFR、GARFT基因表达情况,研究各项指标与客观缓解率、总生存期、无进展生存期的关系。结果56例患者客观有效率（完全缓解＋部分缓解）为39.2%（22/56）。中位无进展生存（PFS）为5.7个月（95%CI为5.01～6.40）,中位总生存期（OS）为12.0个月（95%CI为11.10～12.90）。卡方分析结果显示,年龄、淋巴结肿大、远处转移及TS基因扩增与疗效有关。单因素及多因素分析结果显示,是否远处转移、TS表达水平与无进展生存和总生存期相关（P〈0.01）。结论外周血TS可作为预测应用培美曲塞化疗晚期肺癌患者预后的分子标志。

Objective To investigate the effect and prognostic factors of pemetrexed - containing chemotherapy in first - line treatment of advanced non - small cell lung cancer（NSCLC）. Methods A retrospective analysis of 56 Ⅲ B, Ⅳ phase NSCLC patients from March 2008 to March 2010 in Henan Province People＇ s Hospital, who were treated with pemetrexed and cisplatin for first - line was performed. Peripheral blood TS, DHFR, GARFT gene expression were detected, and were studied the rela- tionship of these genes between with response rate, overall survival, and progression - free survival. Chi - square tests was used for analysis of clinical factors associated with chemotherapy, Kaplan - Metier curve and the log - rank test were used for survival analysis. Results 22 patients responsed for the chemotherapy （complete response and partial response ）, the response rate （RR） was 39.2% （22/56）. The median progression - free survival （PFS） was 5.7 months （95 % CI 5.01 - 6.40）, median overall survival （OS） was 12.0 months （95% CI 11. 10 - 12.90）. Chi - square analysis showed that age, lymph nodes, dis- tant metastasis and TS gene amplification related with therapy efficacy. Univariate and multivariate analysis showed that, distant metastasis, TS expression levels （P 〈 0.01 ） were significantly associated with PFS and OS. Conclusion TS may be a valuable genetic marker for pemetrexed - based chemotherapy in NSCLC, and the results still need further confirmation.