EGFR基因突变与酪氨酸激酶抑制剂疗效及预后之间的关系

The Relationship between EGFR Mutations and Response and Prognosis of Tyrosine Kinase Inhibitors in Advanced Non-Small-Cell Lung Cancer

背景与目的表皮生长因子受体（epidermal growth factor receptor，EGFR）信号通路在非小细胞肺癌的发生和发展中起重要作用。EGFR酪氟酸激酶抑制剂（EGFR tyrosine kinase inhibitors，EGFR-TKIs）是目前非小细胞肺癌（NSCLC）治疗的热点。研究表明，EGFR基因突变与TKIs的疗效及预后相关。本研究旨在了解EGFR基因突变与两种酪氨酸激酶抑制剂疗效及预后的相关性。方法共收集了34例接受gefitinib单药治疗和25例接受erlotinib单药治疗的晚期NSCLC患者的病理组织蜡块及相关临床资料。用PCR-PAGE检测EGFR199b显子突变，PCR＊RFLP检测EGFR21外显子突变，均用直接测序进行验证。结合临床进行分析。结果59例NSCLC标本中共检测出22例标本中有EGFR基因突变，突变率为37．3％。EGFR基因突变率在女性、腺癌、不吸烟患者中高（P〈0．05）。有EGFR基因突变的患者接受酪氨酸激酶抑制剂治疗的有效率高于无突变患者（50％vs18．9％，P〈0．05），疾病控制率高于无突变患者（86．4％vs54．1％，P〈0．05）。有EGFR基因突变的患者的疾病进展时间和总生存期均高于无突变患者，但是没有统计学差异（P〉0.05）。结论EGFR基因突变在女性、腺癌和不吸烟者中发生率高。有EGFR基因突变的晚期NSCLC接受EGFR酪氨酸激酶抑制剂治疗的有效率和疾病控制率高于无EGFR基因突变者。

Background and objectives Epigermal growth factor receptor （EGFR） signal pathway plays an important role in the genesis and development of non-small cell lung cancer （NSCLC）. EGFR tyrosine kinase inhibitors （EGFR-TKIs） is currently investigated in the treatment of NSCLC. It was suggested in previous studies that the EGFR gene mutations were correlated with the response to EGFR- TKIs therapy and prognosis of NSCLC. We studied the role of EGFR gene mutations in response to two kinds of TKIs therapy and prognosis of NSCLC. Methods The tissue samples of 59 advanced NSCLC patients （34 patients receiving Gefitinib monotherapy and 25 patients receiving Erlotinib monotherapy） were collected, and patient charts were reviewed. The mutations in exons 19 and 21 of EGFR gene were detected by PCR-PAGE and PCR-RFLP respectively. The sequences of interested fragments were verified by direct sequencing. Relationship between EGFR mutation and response to TKIs therapy was analyzed with x 2 test. Results EGFR gene mutations were identified in 22 of 59 samples （37.3%）. EGFR gene mutation rate was significantly higher in female, non-smoker and patients with adenocarcinoma than in others （50% vs 18.9%, P 〈0.05）. The patients with EGFR gene mutation had a better response to TKIs therapy than those without （86.4% vs 54.1%, P 〈0.05）. The patients with EGFR gene mutation had slower disease progression and longer overall survival than those without, but statistically non-significant （P 〉0.05）. Conclusions EGFR gene mutation occurs more frequently in female, non-smoker and patients with adenocarcinoma. In patients with advanced NSCLC, EGFR mutation is associated with good response to EGFR-TKIs therapy.