上海交通大学学报(医学版)

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EGFR野生型NSCLC患者ERCC1RRM1TYMSTUBB3 mRNA表达水平对化疗效果和预后的影响

石琴,陈群,谢强,肖松,林江平,王成辉   

  1. 福建省福州肺科医院肿瘤内科, 福州 350008
  • 出版日期:2015-07-28 发布日期:2015-08-27
  • 作者简介:石琴(1976—), 女, 副主任医师, 学士; 电子信箱: 13600868810@139.com。
  • 基金资助:

    福州市科技计划项目(2011-S-68-2)

Effects of mRNA expressions of ERCC1, RRM1, TYMS, and TUBB3 of NSCLC patients with wild-type EGFR on efficacy and prognosis of chemotherapy

SHI Qin, CHEN Qun, XIE Qiang, XIAO Song, LIN Jiang-ping, WANG Cheng-hui   

  1. Department of Oncology, Fuzhou Pulmonary Hospital of Fujian, Fuzhou 350008, China
  • Online:2015-07-28 Published:2015-08-27
  • Supported by:

    Fuzhou Science and Technology Project, 2011-S-68-2

摘要:

目的  联合检测EGFR野生型非小细胞肺癌(NSCLC)患者的ERCC1、RRM1、TYMSTUBB3的mRNA表达水平差异,以探究4种基因的表达水平对化疗效果及预后的影响。方法  将353例NSCLC患者的标本通过xTAG-液相芯片法筛选出EGFR野生型患者,采用实时荧光定量PCR检测标本中4种基因的mRNA表达水平。EGFR野生型患者中4种基因均高表达的为高表达组,否则为低表达组,比较两组患者接受化疗后的中位无进展生存期及中位总生存期。结果  遴选出EGFR野生型NSCLC患者227例,除吸烟与不吸烟者外,其他不同特征型患者之间4种基因mRNA表达水平之间差异无统计学意义(P>0.05)。野生型高表达组有27例,野生型低表达组有53例,两组患者客观缓解率(ORR)(14.8%  vs  41.5%,P<0.05)、疾病控制率(DCR)(40.7% vs 811%,P<0.05)、中位无进展生存期(月)(3.3 vs 4.9,P=0.001)与中位总生存期(月)(7.1  vs  8.1,P=0.048)间差异均有统计学意义。Cox多因素分析显示,4种基因高表达为EGFR野生型NSCLC患者化疗预后的独立危险因素(HR=1.92;95%CI: 1.10~3.42)。结论  EGFR野生型NSCLC患者肿瘤组织的ERCC1、TYMS、TUBB3RRM1 mRNA为高表达水平时,预示其对化疗药物具有耐药性。联合检测4种基因的表达有利于化疗方案的选择。

关键词: 非小细胞肺癌, 表皮生长因子受体, 野生型, ERCC1, RRM1, TYMS, TUBB3

Abstract:

Objective  To jointly detect the differences of mRNA expressions of ERCC1, RRM1, TYMS, and TUBB3 of non-small cell lung cancer (NSCLC) patients with wild type epidermal growth factor receptor (EGFR) and explore the effects of expressions of 4 genes on the efficacy and prognosis of chemotherapy. Methods  Patients with wild type EGFR were screened by xTAG liquid phase chip method from samples of 353 NSCLC patients. The mRNA expression levels of 4 genes were detected by real-time PCR. Patients with wild type EGFR were divided into the high expression group (expressions of 4 genes were high) and low expression group (expressions of 4 genes were low). The median progression free survival and median overall survival of two groups were compared after chemotherapy. Results  A total of 227 NSCLC patients with wild type EGFR were screened. The differences of mRNA expression levels of 4 genes of patients were not statistically significant (P>0.05) except differences between smoking and non-smoking patients. There were 27 patients in the high expression group and 53 patients in the low expression group. The differences of the objective remission rate (ORR) (14.8% vs 41.5%, P<0.05), disease control rate (DCR) (40.7% vs 81.1%, P<0.05), median progression free survival (3.3 m vs 4.9 m, P=0.001), and median overall survival (7.1 m vs 8.1 m, P=0.048) of two groups were statistically significant. Cox multivariate analysis showed that the high expression of 4 genes was independent risk factor of prognosis for NSCLC patients with wild type EGFR after chemotherapy (HR=1.92;95%CI: 1.10-3.42). Conclusion  High mRNA expressions of ERCC1, TYMS, TUBB3, and RRM1 in cancer tissue of NSCLC patients with wild type EGFR indicate that they are resistant to chemotherapeutic drugs. Joint detection of expressions of 4 genes is helpful for choosing chemotherapy plans.

Key words: non-small cell lung cancer, epidermal growth factor receptor, wild type, ERCC1, RRM1, TYMS, TUBB3