BIM缺失多态性和BIM表达作为预测生物标志物在EGFR阳性非小细胞肺癌中最大化EGFR-TKI治疗获益的作用
Role of BIM Deletion Polymorphism and BIM Expression as Predictive Biomarkers to Maximize the Benefit of EGFR-TKI Treatment in EGFR-Positive NSCLC.
作者信息
Incharoen Pimpin, Charonpongsuntorn Chanchai, Saowapa Sakditat, Sirachainan Ekaphop, Dejthevaporn Thitiya, Kampreasart Kaettipong, Trachu Narumol, Muntham Dittapol, Reungwetwattana Thanyanan
机构信息
Department of Pathology, Faculty of Medine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
出版信息
Asian Pac J Cancer Prev. 2019 Dec 1;20(12):3581-3589. doi: 10.31557/APJCP.2019.20.12.3581.
OBJECTIVE
BIM is a modulator of apoptosis that is triggered by EGFR-TKIs. This study evaluated the role of BIM deletion and its expression as predictor of EGFR-TKI treatment outcome.
METHODS
The medical record of 185 EGFR-positive advanced non-small cell lung cancer (NSCLC) patients with/ without EGFR-TKI treatment between 9/2012 and 12/2014 were retrospectively reviewed. BIM deletion polymorphism and expression were tested by RT-PCR and immunohistochemistry, respectively. Survival outcomes in EGFR-TKI-treated patients were analyzed according to treatment sequence and EGFR mutation. The correlation between BIM deletion polymorphism, expression, response rate (as a function of EGFR-TKI treatment) and schedule was also explored.
RESULT
EGFR-TKIs were administered to 139 (75.1%) of the 185 patients: as the first-line in 52 (37.4%) patients and as later-line treatment in 87 (62.6%) patients. Median overall survival (mOS) was significantly longer in EGFR-TKIs treated patients (28.9 vs. 7.4 months, P<0.001). Among L858R-mutated patients, median progression-free survival (mPFS) was significantly longer in first-line EGFR TKI treatment than a later-line (12.6 vs. 6.3 months, P=0.03). BIM deletion polymorphism and expression was detected in 20.2% and 52.7%, respectively. Patients without BIM deletion polymorphism had a significantly longer mOS when treated with a first-line than with a later-line EGFR-TKI (28.9 vs. 20.7 months, P= 0.04). Patients without BIM expression had a significantly longer mPFS (9.6 vs. 7.3 months, P=0.01) better mOS and response rate (RR).
CONCLUSION
BIM deletion polymorphism and expression may predict an EGFR-TKI response in patients with EGFR-positive during therapy.
目的
BIM是一种由表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）触发的细胞凋亡调节因子。本研究评估了BIM缺失及其表达作为EGFR-TKI治疗结果预测指标的作用。
方法
回顾性分析了2012年9月至2014年12月期间185例接受或未接受EGFR-TKI治疗的EGFR阳性晚期非小细胞肺癌（NSCLC）患者的病历。分别采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学检测BIM缺失多态性和表达情况。根据治疗顺序和EGFR突变情况分析EGFR-TKI治疗患者的生存结局。还探讨了BIM缺失多态性、表达、缓解率（作为EGFR-TKI治疗的函数）与治疗方案之间的相关性。
结果
185例患者中有139例（75.1%）接受了EGFR-TKIs治疗：52例（37.4%）患者作为一线治疗，87例（62.6%）患者作为二线及后续治疗。接受EGFR-TKIs治疗的患者中位总生存期（mOS）显著更长（28.9个月对7.4个月，P<0.001）。在L858R突变患者中，一线EGFR-TKI治疗的中位无进展生存期（mPFS）显著长于二线及后续治疗（12.6个月对6.3个月，P=0.03）。BIM缺失多态性和表达的检测率分别为20.2%和52.7%。无BIM缺失多态性的患者接受一线EGFR-TKI治疗时的mOS显著长于二线及后续治疗（28.9个月对20.7个月，P=0.04）。无BIM表达的患者mPFS显著更长（9.6个月对7.3个月，P=0.01），总生存期和缓解率（RR）更好。
结论
BIM缺失多态性和表达可能预测EGFR阳性患者在治疗期间对EGFR-TKI的反应。
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