Bcl-2-like protein 11 deletion polymorphism predicts survival in advanced non-small-cell lung cancer
Journal
Journal of Thoracic Oncology
Journal Volume
9
Journal Issue
9
Pages
1385-1392
Date Issued
2014
Author(s)
Lin Y.-L.
Hsu W.-H.
Chen H.-Y.
Abstract
INTRODUCTION: Germline Bcl-2-like protein 11 (BIM) deletion polymorphism in Asian is a poor predictive factor for treatment outcomes to tyrosine kinase inhibitors (TKIs) in malignancies. We explored the impact of BIM deletion polymorphism on treatment outcome of advanced non-small-cell lung cancer (NSCLC). METHODS: We prospectively collected tissue samples, blood, and clinical data from two cohorts of advanced NSCLC patients. BIM deletion polymorphism was correlated with overall survival (OS) and progression-free survival (PFS) to epidermal growth factor receptor (EGFR) TKIs and chemotherapy treatment. RESULTS: BIM deletion polymorphism was detected in blood of 16.2% (33 of 204) patients. The PFS to first-line EGFR-TKIs in 153 patients were 8.6 and 4.6 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.004). Among 120 patients who received chemotherapies, the PFS to chemotherapies were 5.6 and 3.5 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.050). The OS of all 204 patients was 24.8 and 16.8 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.005). Multivariate analyses suggested that BIM deletion polymorphism was an independent predictor for shorter PFS to EGFR-TKIs (hazard ratio [HR] 2.15, p = 0.002), PFS to chemotherapy (HR 2.40, p = 0.016), and OS (HR 1.65, p = 0.039). CONCLUSIONS: BIM deletion polymorphism predicts shorter PFS to EGFR-TKIs and OS in advanced NSCLC. Copyright ? 2014 by the International Association for the Study of Lung Cancer.
SDGs
Other Subjects
BIM protein; epidermal growth factor receptor; gefitinib; protein bcl 2; protein tyrosine kinase inhibitor; apoptosis regulatory protein; Bcl-2-like protein 11; DNA; membrane protein; oncoprotein; adult; advanced cancer; article; blood; cancer chemotherapy; clinical trial (topic); DNA polymorphism; female; gene deletion; human; lung non small cell cancer; major clinical study; male; overall survival; predictive value; priority journal; progression free survival; prospective study; tissues; treatment outcome; wild type; disease free survival; epidemiology; follow up; gene deletion; genetic polymorphism; genetics; lung tumor; metabolism; middle aged; mortality; mutation; non small cell lung cancer; nucleotide sequence; polymerase chain reaction; prognosis; survival rate; Taiwan; trends; Apoptosis Regulatory Proteins; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; DNA Mutational Analysis; DNA, Neoplasm; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Membrane Proteins; Middle Aged; Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Prognosis; Prospective Studies; Proto-Oncogene Proteins; Sequence Deletion; Survival Rate; Taiwan
Publisher
Lippincott Williams and Wilkins
Type
journal article