title: An intronic polymorphism in GRP78 improves chemotherapeutic prediction in non-small cell lung cancer.
abstract: BACKGROUND
  Glucose-regulated protein 78 (GRP78) is involved in not only the progression of non-small cell lung cancer (NSCLC) but also chemotherapeutic effects. We hypothesized that an intronic polymorphism (rs430397G>A) in GRP78 affects survival among patients with NSCLC treated with platinum-based chemotherapy.
  
  
  METHODS
  Blood samples of patients with advanced NSCLC (IIIB/IV) were maintained in our specimen bank between 2001 and 2006. Genomic DNA was genotyped for rs430397. Associations between rs430397 and platinum-based treatment response, overall survival (OS), NSCLC-related survival, progression-free survival (PFS), and relapses were evaluated. GRP78 RNA and protein in NSCLC tissues were tested by real-time polymerase chain reaction and immunohistochemistry.
  
  
  RESULTS
  The AA genotype is significantly associated with platinum-based chemoresistance (P = .019) and NSCLC-related death (P = .022). OS, NSCLC-related survival, and PFS of the AA genotype group are decreased compared with the GG and AG genotype groups (log-rank P < .05, respectively). The AA group showed a higher prevalence of early NSCLC relapses than the AG and GG group (P = .030). In addition, the AA genotype showed a significantly increased risk for OS (hazard ratio, 1.95) and PFS (hazard ratio, 1.80) compared with the GG group. Functional analysis showed that NSCLC tissues with genotype AA have higher GRP78 RNA and protein expression compared with those carrying GG at rs430397.
  
  
  CONCLUSIONS
  The rs430397 AA genotype of GRP78 is associated with reduced survival and higher prevalence of early relapses in patients with advanced NSCLC treated with platinum-based chemotherapy.
authors.affiliation: Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, China; Cancer Institute, Affiliated Tumor Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Marie C M
authors.initials: MCM
authors.lastname: Lin
authors.affiliation: Department of Oral Anatomy and Physiology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wenguo
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Epidemiology, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Linwei
authors.initials: L
authors.lastname: Tian
authors.affiliation: Cancer Institute, Affiliated Tumor Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Ng
authors.affiliation: Cancer Institute, Affiliated Tumor Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Li Ka Shing Institute of Medical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Hsiangfu
authors.initials: H
authors.lastname: Kung
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. Electronic address: lidp@mail.sysu.edu.cn.
authors.forename: Dongpei
authors.initials: D
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000627:therapeutic use; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D002945:Cisplatin