【摘要】 目的通过检测BCL-2基因多态性,探讨其与复治晚期非小细胞肺癌表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI)治疗疗效的关系。方法 116例复治晚期非小细胞肺癌患者,既往均接受过化疗,失败后接受吉非替尼或厄洛替尼靶向治疗。采用多聚酶链反应方法检测患者外周血白细胞中BCL-2基因多态性。结果 116例患者总有效率为25.9%,BCL-2各基因型间患者间的有效率无明显差异。相比BCL-2其它基因型,AA型疾病控制率更低(40%vs 75.2%,P=0.005)。单因素分析中位PFS,AA型中位无进展时间短于其它基因型(2.6个月vs 6.0个月,P=0.025),而女性长于男性(10.2个月vs 4.6个月,P=0.04);不吸烟者长于有吸烟史者(11.9个月vs2.5个月,P=0.000);病理类型为腺癌长于其他类型(11.9个月vs 4.1个月,P=0.000),均达到统计学差异。多因素分析结果显示,包括性别、吸烟史、ECOG评分和病理类型,BCL-2基因多态性为PFS的独立预后因素(P=0.049)。结论复治晚期EGFR突变状态未明的非小细胞肺癌BCL-2(-938C>A)基因型为AA者是提示近期疗效较差的指标。更多还原

【Abstract】 Objective To investigate the association between BCL-2 gene polymorphism and therapeutic efficacy of tyrosine kinase inhibitor(TKI) in pretreated patients with advanced non-small cell lung cancer(NCSLC).Methods A total of 116 patients with advanced NSCLC were recruited from Zhejiang Cancer Hospital,all of whom were treated with gefitinib or erlotinib after failure to chemotherapy.BCL-2 gene polymorphism of peripheral blood lymphocytes was detected with polymerase chain reaction(PCR).Statistical analysis was performed by SPSS version 13.0.Results The overall response rate was 28.9%.No significant association was found between BCL-2(-938C>A) polymorphism and the objective response rate.The disease control rate of patients with BCL-2AA genotype was lower than that of patients with genotype CC or CA(40% vs 75.2%,P=0.005).Univariate analysis identified gender,smoking history,histology and BCL-2(-938 C >A) polymorphism as predictive markers of progress free survival(PFS)(P=0.04,P=0.000,P=0.000 and P=0.05).Multivariate analysis demonstrated that BCL-2(-938 C >A) polymorphism was correlated independently with PFS(P=0.049).Conclusion Our data suggest that BCL-2(-938C>A) AA genotype may be a predictive marker for poor DCR and PFS in advanced NSCLC patients treated with tyrosine kinase inhibitor.更多还原