Association between GNAS1 T393C Polymorphism and Therapeutic Efficacy of Tyrosine Kinase Inhibitor in Pretreated Advanced Non-small Cell Lung Cancer with Unknown EGFR Mutation Status

• Main Authors: Wei HONG, Baochai LIN, Beibei ZHANG, Weimin MAO, Yiping ZHANG
• Format: Article
• Language: zho
• Published: Chinese Anti-Cancer Association; Chinese Antituberculosis Association 2014-04-01
• Series: Chinese Journal of Lung Cancer
• Subjects: GNAS1 Gene; Polymorphism; Lung neoplasms; Tyrosine kinase inhibitor
• Online Access: http://dx.doi.org/10.3779/j.issn.1009-3419.2014.04.06

Background and objective Epidermal growth factor receptor (EGFR)-activating mutation predicts excellent response to EGFR tyrosine kinase inhibitors (TKIs). However, lung cancer patients are often 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 efficacy 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 gefitinib or erlotinib after 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 The overall response rate was 29.3%. No significant associations were found among GNAS1 T393C polymorphism and the objective response rate. The 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 identified gender, smoking history, histology 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 demonstrated 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.