Background and objective: BIM gene is a member of the BCL-2 family, is involved in cell death. The aim of this study is to explore the relationship between BIM gene polymorphism and therapeutic efficacy in the retreatment advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitor (EGFR-TKI).
Methods: In the study, there were 123 patients who were diagnosed with advanced NSCLC in Zhejiang Province Cancer Hospital between January 2009 to October 2012, all of who were received gefitinib and erlotinib therapy after failure to chemotherapy. We detected the genotype of peripheral blood leukocytes of patients with BIM gene polymorphism though polymerase chain reaction (PCR). Statistical analysis was performed by SPSS version 13.0.
Results: On the disease control rates, BIM gene with no polymorphism type was slightly better trend than polymorphism types in disease control rate DCR (75.5% vs 57.1%, χ²=2.931, P=0.087). Univariate analysis the median PFS, women were longer than men (6.9 months vs 4.5 months, χ² =7.077, P=0.008). Non-smokers were longer than smokers (8.0 months vs 2.5 months, χ² =15.277, P<0.001). Adenocarcinoma were longer than others pathological type (7.0 months vs 2.0 months, χ² =14.978, P<0.001). The median PFS in BIM gene with no polymorphism type were longer than with polymorphism type (6.0 months vs 3.5 months, χ²=7.035, P=0.008). Multi-factor analysis showed that smoking, pathological type, the BIM gene polymorphism were the independent prognostic factors for PFS.
Conclusions: The patients with the BIM gene no polymorphism have longer the median progression-free time than the polymorphism types in retreatment advanced non-small cell lung cancer patients with tyrosine kinase inhibitor.
背景与目的 BIM基因是BCL-2家族成员之一，是参与细胞死亡的重要介质。在非小细胞肺癌（non-small cell lung cancer, NSCLC）中，BCL-2家族成员蛋白介导的EGFR基因突变癌细胞能够激活PI3K/AKT/mTORC和MER/ERT信号通道，决定着细胞的存活或者凋亡。BIM基因的BH3域缺失，则容易引起凋亡受阻。本研究通过检测BIM基因多态性，探讨其与复治晚期NSCLC表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitor, EGFR-TKI）治疗疗效的关系。方法 入选2009年1月1日-2012年10月1日就诊于浙江省肿瘤医院的123例复治晚期NSCLC患者，所有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BIM基因多态性。采用SPSS 13.0统计软件分析。结果 在疾病控制率上， BIM基因无多态性的患者较BIM基因有多态性的患者呈略好趋势（DCR 75.5% vs 57.1%, χ2=2.931, P=0.087）。单因素分析中位PFS，女性长于男性（6.9个月 vs 4.5个月，χ2=7.077，P=0.008)；不吸烟者长于有吸烟史者（8.0个月 vs 2.5个月，χ2=15.277，P<0.001)；病理类型为腺癌的长于其它类型（7.0个月 vs 2.0个月，χ2 =14.978，P<0.001)； BIM基因无多态性的患者中位PFS长于BIM基因有多态性的患者（6.0个月 vs 3.5个月，χ2 =7.035，P=0.008)。多因素分析结果显示吸烟、病理类型、BIM基因多态性为影响PFS的预后因素。BIM基因型与不良反应差异无统计学意义（P>0.05）。结论 BIM基因多态性的有无对复治晚期NSCLC EGFR-TKI治疗患者的中位无进展时间有统计学差异，检测患者BIM基因多态性对复治晚期NSCLC EGFR-TKI治疗患者的评估预后有重要意义。