Jupeng Yuan1, Bo Li2, Nasha Zhang1, Hui Zhu1, Liqing Zhou3, Li Zhang4, Ming Yang5. 1. Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China. 2. Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 3. Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, China. 4. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: luzigang@163.com. 5. Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China. Electronic address: yangm@sdu.edu.cn.
Abstract
BACKGROUND: Proapoptotic protein Bcl-2-like 11 (BIM) is a crucial tumor suppressor gene in lung cancer development. A 2903-bp genomic deletion polymorphism is present in BIM intron 2, which alters RNA splicing and impairs the generation of the death-inducing isoform of BIM and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In the present study, we investigated the clinical implications of this genetic polymorphism in patients with advanced lung adenocarcinoma treated with gefitinib. MATERIALS AND METHODS: After genotyping the BIM deletion polymorphism in 111 patients with stage IIIB or IV lung adenocarcinoma receiving gefitinib, the hazard ratio (HR) and 95% confidence interval (CI) for progression-free survival and overall survival were estimated using Cox proportional hazards models. RESULTS: Possession of ≥ 1 deletion allele of the BIM polymorphism was observed in 18.02% of the patients. The BIM deletion polymorphism was an independent indicator of a shorter PFS (7.5 months vs. 11.3 months; HR, 2.38; 95% CI, 1.30-4.34; P = .005) and shorter OS (9.9 months vs. 27.5 months; HR, 2.53; 95% CI, 1.37-4.65; P = .003). Additionally, patients carrying the BIM deletion allele were more likely to experience acquired gefitinib-resistant disease. CONCLUSION: Our results indicate that the BIM deletion polymorphism might be a promising germline biomarker for gefitinib treatment in Chinese patients with lung adenocarcinoma.
BACKGROUND: Proapoptotic protein Bcl-2-like 11 (BIM) is a crucial tumor suppressor gene in lung cancer development. A 2903-bp genomic deletion polymorphism is present in BIM intron 2, which alters RNA splicing and impairs the generation of the death-inducing isoform of BIM and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In the present study, we investigated the clinical implications of this genetic polymorphism in patients with advanced lung adenocarcinoma treated with gefitinib. MATERIALS AND METHODS: After genotyping the BIM deletion polymorphism in 111 patients with stage IIIB or IV lung adenocarcinoma receiving gefitinib, the hazard ratio (HR) and 95% confidence interval (CI) for progression-free survival and overall survival were estimated using Cox proportional hazards models. RESULTS: Possession of ≥ 1 deletion allele of the BIM polymorphism was observed in 18.02% of the patients. The BIM deletion polymorphism was an independent indicator of a shorter PFS (7.5 months vs. 11.3 months; HR, 2.38; 95% CI, 1.30-4.34; P = .005) and shorter OS (9.9 months vs. 27.5 months; HR, 2.53; 95% CI, 1.37-4.65; P = .003). Additionally, patients carrying the BIM deletion allele were more likely to experience acquired gefitinib-resistant disease. CONCLUSION: Our results indicate that the BIM deletion polymorphism might be a promising germline biomarker for gefitinib treatment in Chinese patients with lung adenocarcinoma.
Authors: Xi Lei; Shuai Zhu; Dian Ren; Fan Ren; Tong Li; Ning Zhou; Shuo Li; Tao Shi; Lingling Zu; Zuoqing Song; Justyna Chalubinska-Fendler; Marc G Denis; Eric H Bernicker; Vincent Thomas de Montpréville; Richeng Jiang; Song Xu Journal: Transl Lung Cancer Res Date: 2022-06
Authors: Yuhong Lu; Yanfeng Liu; Sebastian Oeck; Gary J Zhang; Alexander Schramm; Peter M Glazer Journal: Cancer Res Date: 2020-09-01 Impact factor: 12.701