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Title: Role of BIM deletion polymorphism and BIM expression as predictive biomarkers to maximize the benefit of EGFR-TKI treatment in EGFR-Positive NSCLC
Authors: Pimpin Incharoen
C. Charonpongsuntorn
Chanchai Sakditad Saowapa
Ekaphop Sirachainan
Thitiya Dejthevaporn
Kaettipong Kampreasart
Narumol Trachu
Dittapol Muntham
Thanyanan Reungwetwattana
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Mahidol University
Srinakharinwirot University
Rajamangala University of Technology Suvarnabhumi
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 1-Jan-2019
Citation: Asian Pacific Journal of Cancer Prevention. Vol.20, No.12 (2019), 3581-3589
Abstract: © 2019, Asian Pacific Organization for Cancer Prevention. 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.
ISSN: 2476762X
Appears in Collections:Scopus 2019

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