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
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 tumo...
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Chinese Anti-Cancer Association; Chinese Antituberculosis Association
2014-04-01
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doaj-96ed8624976d46c78e4fa7e111f9939e2020-11-24T21:59:52ZzhoChinese Anti-Cancer Association; Chinese Antituberculosis AssociationChinese Journal of Lung Cancer1009-34192014-04-0117432132610.3779/j.issn.1009-3419.2014.04.06Association between GNAS1 T393C Polymorphism and Therapeutic Efficacy of Tyrosine Kinase Inhibitor in Pretreated Advanced Non-small Cell Lung Cancer with Unknown EGFR Mutation StatusWei HONG0Baochai LIN1Beibei ZHANG2Weimin MAO3Yiping ZHANG4Zhejiang Cancer Hospital, Zhejiang Key Laboratory of the Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou 310022, ChinaDepartment of Medical Oncology, the First Affiliated Hospital of WenZhou Medical College, Wenzhou 325000, ChinaThe Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaZhejiang Cancer Hospital, Zhejiang Key Laboratory of the Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou 310022, ChinaZhejiang Cancer Hospital, Zhejiang Key Laboratory of the Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou 310022, ChinaBackground 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.http://dx.doi.org/10.3779/j.issn.1009-3419.2014.04.06GNAS1 GenePolymorphismLung neoplasmsTyrosine kinase inhibitor |
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DOAJ |
language |
zho |
format |
Article |
sources |
DOAJ |
author |
Wei HONG Baochai LIN Beibei ZHANG Weimin MAO Yiping ZHANG |
spellingShingle |
Wei HONG Baochai LIN Beibei ZHANG Weimin MAO Yiping ZHANG 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 Chinese Journal of Lung Cancer GNAS1 Gene Polymorphism Lung neoplasms Tyrosine kinase inhibitor |
author_facet |
Wei HONG Baochai LIN Beibei ZHANG Weimin MAO Yiping ZHANG |
author_sort |
Wei HONG |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Chinese Anti-Cancer Association; Chinese Antituberculosis Association |
series |
Chinese Journal of Lung Cancer |
issn |
1009-3419 |
publishDate |
2014-04-01 |
description |
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. |
topic |
GNAS1 Gene Polymorphism Lung neoplasms Tyrosine kinase inhibitor |
url |
http://dx.doi.org/10.3779/j.issn.1009-3419.2014.04.06 |
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