Xiao Zhu1, Marie C M Lin2, Wenguo Fan3, Linwei Tian4, Jinlong Wang5, Samuel S Ng6, Min Wang5, Hsiangfu Kung7, Dongpei Li8. 1. 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. 2. Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. 3. 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. 4. Department of Epidemiology, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China. 5. Cancer Institute, Affiliated Tumor Hospital, Guangzhou Medical University, Guangzhou, China. 6. School of Biological Sciences, The University of Hong Kong, Hong Kong, China. 7. Li Ka Shing Institute of Medical Sciences, The Chinese University of Hong Kong, Hong Kong, China. 8. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. Electronic address: lidp@mail.sysu.edu.cn.
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.
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: Simon Williams; Hugo Layard Horsfall; Jonathan P Funnell; John G Hanrahan; Danyal Z Khan; William Muirhead; Danail Stoyanov; Hani J Marcus Journal: Cancers (Basel) Date: 2021-10-07 Impact factor: 6.639
Authors: Philippe Rochigneux; Alejandro J Garcia; Brice Chanez; Anne Madroszyk; Daniel Olive; Edward B Garon Journal: Front Immunol Date: 2020-06-24 Impact factor: 7.561