表皮生长因子受体基因CA简单重复序列多态性与晚期小细胞肺癌患者表皮生长因子受体酪氨酸激酶抑制剂临床疗效间的关系  

Correlation of CA-simple sequence repeat polymorphism of epidermal growth factor receptor gene with clinical outcome of patients with advanced non-small cell lung cancer after treatment with epidermal growth factor receptor tyrosine kinase inhibitors

作　　者：周崧雯[1,2] 徐清华[1,2] 张颉[1,2] 邓沁芳[1,2] 任胜祥[1,2] 周彩存[1,2] 

机构地区：[1]同济大学附属上海市肺科医院肿瘤科 [2]同济大学医学院肿瘤研究所,上海200433

出　　处：《肿瘤》2011年第7期633-637,共5页Tumor

基　　金：上海市卫生局青年科研项目(编号:2007Y51)

摘　　要：目的:研究表皮生长因子受体(epidermal growth factor receptor,EGFR)基因第1内含子区CA简单重复序列(simple sequence repeat,SSR)多态性与晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者应用表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)治疗的临床疗效间的关系。方法:观察101例晚期NSCLC患者使用EGFR-TKIs的临床疗效及生存情况,通过对患者EGFR-TKIs治疗前外周血进行EGFR基因第1内含子的PCR扩增,并对PCR扩增产物直接进行序列测定,分析CA-SSR多态性与EGFR-TKIs治疗的临床疗效和患者生存情况间的关系。结果:EGFR-TKIs治疗后,24例(23.8%)患者部分缓解(partial response,PR),46例(45.5%)患者为疾病稳定(stable disease,SD),临床受益(PR+SD)患者为70例(69.3%)。腺癌和女性患者的中位生存期(median survival time,MST)较非腺癌和男性患者明显延长(P<0.05)。CA-SSR出现频率最多的CA等位基因为(CA)20[68.7%(68/99)],短CA-SSR组患者经EGFR-TKIs治疗后的无进展生存(progression-free survival,PFS)时间比长CA-SSR患者明显延长(P=0.039);短CA-SSR组MST为15.7个月,长CA-SSR组MST为14.4个月,组间差异无统计学意义(P=0.691)。结论:EGFR-TKIs治疗可明显延长腺癌、女性NSCLC患者的MST和短CA-SSR患者的PFS。Objective： To investigate the correlation of CA-simple sequence repeat （SSR） polymorphism of epidermal growth factor receptor （EGFR） gene with the clinical outcome of patients with advanced non-small cell lung cancer （NSCLC） after treatment with epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs）. Methods： The clinical outcome and the survival of 101 patients with advanced NSCLC after treatment with EGFR-TKIs were measured. CA-SSR polymorphisim of EGFR intron 1 from peripheral blood cells of NSCLC patients was detected by PCR and direct DNA sequencing. The correlations of CA-SSR polymorphisim with the clinical outcome and the survival of NSCLC patients after treatment with EGFR-TKIs were analyzed. Results： Twenty-four patients reached a partial response （23.8%）, 46 patients reached a stable disease （45.5%）, and 70 patients reached a clinical benefit （69.3%）. Median survival time （MST） in female or adenocarcinoma patients was longer than that in male or non- adenocarcinoma patients （P〈O.05）. Allele （CA）20was the most frequent allele （68.7%, 68/99） in CA-SSR. Progression-free survival （PFS） in patients with short CA-SSR was longer than that in patients with long CA-SSR （P=0.039）. The MSTs of patients with short CA-SSR and long CA-SSR were 15.7 and 14.4 months, respectively, and the difference in MST was not significant （P = 0.691）. Conclusion： The MST of female or adenocarcinoma patients with NSCLC as well as the PSF of patients with short CA-SSR can be prolonged after treatment with EGFR-TKIs.

关 键 词：癌 非小细胞肺 受体 表皮生长因子 多态现象 单核苷酸 表皮生长因子受体酪氨酸激酶抑制剂 

分 类 号：R734.2[医药卫生—肿瘤]