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An intronic polymorphism in GRP78 improves chemotherapeutic prediction in non-small cell lung cancer
2012-06-20 14:10点击:83次发表评论
作者:Zhu, X., Lin, M.C.M., Fan, W., Tian, L., Wang, J.,
机构: 广东医学院生物化学与分子生物学研究所 广东省医学分子影像重点实验室
期刊: CHEST2012年6月6期141卷

Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, China

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 immunohisto chemistry. 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.

通讯作者:Li, D.; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; email: lidp@mail.sysu.edu.cn
学科代码:消化病学   关键词:GRP78的一种内含子多态性可改善非小细胞肺癌的化疗预测
来源: Scopus
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