Qian Zou1, Ping Zhan1, Tangfeng Lv1, Yong Song1. 1. Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medical, Nanjing 210002, China.
Abstract
BACKGROUND: BIM deletion polymorphism is a germline that might lead to little or no BH3 expression, which affects epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) related apoptosis. Recent studies show that BIM deletion polymorphism might be a critical factor leading to the resistance of EGFR-TKIs in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. METHODS: Thus, a meta-analysis was conducted by combing seven original eligible studies including 778 NSCLC patients to investigate a steady and reliable conclusion. RESULTS: Our study indicated that BIM deletion polymorphism was significantly associated with the poor objective response rate (ORR) of EGFR-TKIs in EGFR-mutated NSCLC patients [odds ratios (OR) =0.55, 95% confidence interval (CI), 0.33-0.92]. And disease control rate (DCR) in EGFR-mutate NSCLC patients treated with EGFR-TKIs was significantly decreased in patients with BIM deletion polymorphism (OR=0.55, 95% CI, 0.27-1.12). Moreover, the progression-free survival (PFS) of patients with BIM deletion polymorphism is shorter. CONCLUSIONS: These findings suggested that BIM deletion polymorphism might be a genetic cause of intrinsic resistance to TKI therapy and it could be emerged as an independent predictor to identify patients who would benefit from TKI targeted therapy in EGFR-mutated NSCLC.
BACKGROUND: BIM deletion polymorphism is a germline that might lead to little or no BH3 expression, which affects epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) related apoptosis. Recent studies show that BIM deletion polymorphism might be a critical factor leading to the resistance of EGFR-TKIs in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. METHODS: Thus, a meta-analysis was conducted by combing seven original eligible studies including 778 NSCLCpatients to investigate a steady and reliable conclusion. RESULTS: Our study indicated that BIM deletion polymorphism was significantly associated with the poor objective response rate (ORR) of EGFR-TKIs in EGFR-mutated NSCLCpatients [odds ratios (OR) =0.55, 95% confidence interval (CI), 0.33-0.92]. And disease control rate (DCR) in EGFR-mutate NSCLCpatients treated with EGFR-TKIs was significantly decreased in patients with BIM deletion polymorphism (OR=0.55, 95% CI, 0.27-1.12). Moreover, the progression-free survival (PFS) of patients with BIM deletion polymorphism is shorter. CONCLUSIONS: These findings suggested that BIM deletion polymorphism might be a genetic cause of intrinsic resistance to TKI therapy and it could be emerged as an independent predictor to identify patients who would benefit from TKI targeted therapy in EGFR-mutated NSCLC.
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