title: Bcl-2-like protein 11 deletion polymorphism predicts survival in advanced non-small-cell lung cancer.
abstract: BACKGROUND
  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.
authors: *Department of Oncology; †National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital; ‡Graduate Institute of Oncology and Cancer Research Center; §Graduate Institute of Clinical Medicine; ‖College of Medicine; ¶College of Life Science, National Taiwan University; #Institute of Statistical Science, Academia Sinica; **Department of Medical Imaging; and ††Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
authors: Jih-Hsiang
authors: JH
authors: Lee
authors: Yu-Lin
authors: YL
authors: Lin
authors: Wei-Hsun
authors: WH
authors: Hsu
authors: Hsuan-Yu
authors: HY
authors: Chen
authors: Yeun-Chung
authors: YC
authors: Chang
authors: Chong-Jen
authors: CJ
authors: Yu
authors: Jin-Yuan
authors: JY
authors: Shih
authors: Chia-Chi
authors: CC
authors: Lin
authors: Kuan-Yu
authors: KY
authors: Chen
authors: Chao-Chi
authors: CC
authors: Ho
authors: Wei-Yu
authors: WY
authors: Laio
authors: Pan-Chyr
authors: PC
authors: Yang
authors: James Chih-Hsin
authors: JC
authors: Yang
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D015996:Survival Rate / Q000639:trends; D013624:Taiwan / Q000453:epidemiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D004273:DNA, Neoplasm; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins