Association between GNAS1 T393C Polymorphism and Therapeutic Efifcacy of Tyrosine Kinase Inhibitor in Pretreated Advanced Non-small Cell Lung Cancer with Unknown EGFR Mutation Status
10.3779/j.issn.1009-3419.2014.04.06
- VernacularTitle:GNAS1基因T393C多态性与EGFR突变状态未明复治晚期非小细胞肺癌TKI疗效的关联研究
- Author:
HONG WEI
1
;
LIN BAOCHAI
;
ZHANG BEIBEI
;
MAO WEIMIN
;
ZHANG YIPING
Author Information
1. 310022杭州，浙江省肿瘤医院，浙江省胸部肿瘤诊治技术研究重点实验室
- Keywords:
GNAS1 Gene;
Polymorphism;
Lung neoplasms;
Tyrosine kinase inhibitor
- From:
Chinese Journal of Lung Cancer
2014;(4):321-326
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Epidermal growth factor receptor (EGFR)-activating mutation predicts excellent response to EGFR tyrosine kinase inhibitors (TKIs). However, lung cancer patients are otfen with unknown EGFR mutation status because there are little tumor specimen to determine. TKIs induce tumor cell apoptosis which associates with several apoptosis-related genes. To explore the association between GNAS1 T393C polymorphism and therapeutic effcacy of TKI in pretreated advanced non-small cell lung cancer (NCSLC) with unknown EGFR mutation status. Methods A total of 116 patients were recruited for the study from Zhejiang Cancer Hospital, all of whom were treated with geiftinib or erlotinib atfer failure to prior chemotherapy. We detected the genotype of peripheral blood lymphocytes of patients with GNAS1 T393C polymorphism through polymerase chain reaction (PCR). Statistical analysis was performed by SPSS version 18.0. Results hTe overall response rate was 29.3%. No signiifcant associations were found among GNAS1 T393C polymorphism and the objective response rate. hTe disease control rate of patients with GNAS1 T393C CC genotype was lower than that of patients with variant genotype (TT or CT) (46.2%vs 73.8%, P=0.039). Univariate analysis identiifed gender, smoking history, histol-ogy and GNAS1 T393C polymorphism as predictive marker of PFS (P=0.04, P<0.001, P<0.001 and P=0.005). Multivariate analysis of factors, including smoking history, performance status score, histology, GNAS1 T393C polymorphism demonstrat-ed that GNAS1 T393C polymorphism was correlated independently with PFS (P=0.007). Conclusion Our data suggest the role of GNAS1 T393C CC genotype as a poor predictive marker both of DCR and PFS in advanced NSCLC patients treated with tyrosine kinase inhibitor.
