Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute Beijing, China.
Thorac Cancer. 2014 Nov;5(6):509-16. doi: 10.1111/1759-7714.12119. Epub 2014 Oct 23.
Drug resistance significantly weakens the efficacy of cancer treatment, and the BIM (also known as the BCL2L11 gene) deletion polymorphism has been identified as a potential biomarker for drug resistance. In this retrospective study, we included a total of 290 patients with advanced non-small cell lung cancer (NSCLC) who received treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy.
The BIM deletion polymorphism of each patient was detected by polymerase chain reaction. EGFR mutations were detected by denaturing high-performance liquid chromatography methods and the amplification refractory mutation system.
The BIM deletion polymorphism was detected in 45/290 (15.5%) Chinese NSCLC patients. No associations were observed between the BIM deletion and clinic-pathologic characteristics of patients. The BIM deletion polymorphism was predictive of shorter progression-free survival in Chinese patients with EGFR-mutant adenocarcinoma and who were treated with EGFR-TKIs (7.30 vs. 9.53 months, P = 0.034). Additionally, we found that the BIM deletion polymorphism was an effective predictor of short progression-free survival in individuals with EGFR-mutant NSCLC and treated with chemotherapy containing pemetrexed (3.32 vs. 5.30, P = 0.012) or second-/beyond-line chemotherapy containing taxanes (1.53 vs. 2.61 months, P = 0.025). The BIM deletion was not correlated with overall survival.
The BIM deletion polymorphism occurs in 15.5% of Chinese NSCLC patients, and is a biomarker for resistance to TKIs and chemotherapy. However, BIM deletion was not a decisive factor in overall survival.
耐药性显著削弱了癌症治疗的疗效,而 BIM(也称为 BCL2L11 基因)缺失多态性已被确定为耐药的潜在生物标志物。在这项回顾性研究中,我们共纳入了 290 名接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)和化疗治疗的晚期非小细胞肺癌(NSCLC)患者。
通过聚合酶链反应检测每位患者的 BIM 缺失多态性。通过变性高效液相色谱法和扩增受阻突变系统检测 EGFR 突变。
在中国 NSCLC 患者中检测到 45/290(15.5%)的 BIM 缺失多态性。BIM 缺失与患者的临床病理特征之间未观察到相关性。在接受 EGFR-TKIs 治疗的 EGFR 突变型腺癌中国患者中,BIM 缺失多态性与较短的无进展生存期相关(7.30 与 9.53 个月,P = 0.034)。此外,我们发现 BIM 缺失多态性是接受含培美曲塞的化疗(3.32 与 5.30 个月,P = 0.012)或含紫杉醇的二线/后线化疗(1.53 与 2.61 个月,P = 0.025)的 EGFR 突变型 NSCLC 患者较短无进展生存期的有效预测因子。BIM 缺失与总生存期无关。
在中国 NSCLC 患者中,BIM 缺失多态性发生率为 15.5%,是 TKI 和化疗耐药的生物标志物。然而,BIM 缺失不是总生存期的决定性因素。