title: The T393C polymorphism of GNAS1 as a predictor for chemotherapy sensitivity and survival in advanced non-small-cell lung cancer patients treated with gemcitabine plus platinum.
abstract: OBJECTIVE
  The GNAS1 gene is linked to proapoptotic signaling and correlates closely with clinical outcomes in many human cancers. The aim of this study was to evaluate whether the T393C polymorphism of the GNAS1 gene could be used as a chemotherapy sensitivity and prognosis predictive marker of advanced non-small-cell lung cancer (NSCLC) treated with gemcitabine plus platinum (GP).
  
  
  METHODS
  In this study, we performed the PCR-restriction fragment length polymorphism assay to examine the genotypes of the GNAS1 T393C polymorphism in 131 peripheral blood DNA specimens from advanced NSCLC patients with GP treatment.
  
  
  RESULTS
  The frequencies of the CC, CT, and TT genotypes in 131 advanced NSCLC cases were 25.2, 47.4, and 26.7%, respectively. The favorable TT genotype was significantly correlated with better overall survival (OS; P < 0.05) and longer progress-free survival (PFS; P < 0.05) compared with the CT or CC genotype. In the multivariate Cox proportional hazards model, the GNAS1 T393C polymorphism was independently associated with overall survival after adjusting the clinicopathological factors (P < 0.05).
  
  
  CONCLUSIONS
  This study suggests that the TT genotype of the GNAS1 T393C polymorphism could be an independent prognostic marker to predict chemotherapy sensitivity, favorable OS and PFS in advanced NSCLC patients with GP treatment.
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou City, Zhejiang Province, 310022, China.
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Xie
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Jun-Yan
authors.initials: JY
authors.lastname: Kou
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Lin
authors.initials: L
authors.lastname: Hu
authors.forename: Dan
authors.initials: D
authors.lastname: Hong
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002864:Chromogranins; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D016016:Proportional Hazards Models; D000093542:Gemcitabine
chemical_list: D002864:Chromogranins; D003841:Deoxycytidine; D016190:Carboplatin; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D002945:Cisplatin; D000093542:Gemcitabine