Background: Genetic variations of the epidermal growth factor receptor (EGFR) may alter the protein function and therapeutic efficacy of EGFR inhibitors. The aim of this study is to investigate the association between single nucleotide polymorphism rs2293347 in EGFR and the clinical outcome in patients with advanced non-small cell lung cancer (NSCLC) treated with gefitinib.
Methods: A total of 88 advanced NSCLC patients treated with gefitinib were analyzed in the present study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was conducted to analyze the genotype. The association study was performed between genotypes and clinical efficacy among 88 patients.
Results: rs2293347 was associated with the efficacy of gefitinib. The response rate for the rs2293347 GG was significantly higher than that for the GA or AA (71.4% vs 36.0%, P=0.002). rs2293347 GG genotype was also associated with longer progression-free survival compared with GA or AA genotype (10 months vs 3 months, P=0.005). No significant difference was shown on the overall survival (OS) (P=0.409).
Conclusions: rs2293347 polymorphism in exon 25 is associated with the clinical efficacy of gefitinib and may be a potential biomarker to predict the clinical outcome in advanced NSCLC patients treated with gefitinib.
背景与目的: 表皮生长因子受体（epidermal growth factor receptor, EGFR）基因遗传变异可能影响蛋白的功能，从而影响EGFR抑制剂的疗效，本研究旨在探讨EGFR酪氨酸激酶抑制剂吉非替尼的临床疗效与靶标基因EGFR单核苷酸多态rs2293347之间的相关性。
方法: 对88例接受过吉非替尼治疗的晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者进行分析，采用限制性片断长度多态进行基因分型，分析EGFR基因rs2293347多态与患者临床疗效及预后的关系。
结果: EGFR基因rs2293347多态与吉非替尼的疗效相关，携带GG基因型的患者接受吉非替尼治疗的临床获益率为71.4%，而携带GA/AA基因型的患者仅为36.0%（P=0.002）。GG基因型的患者无进展生存期也明显长于GA/AA基因型的患者（10个月vs 3个月，P=0.005），但是两组的总生存时间（overall survival, OS）无统计学差异（P=0.409）。
结论: EGFR基因rs2293347多态与吉非替尼临床疗效密切相关，可能成为预测吉非替尼疗效的理想的遗传标记物。