[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].

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 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).

CONCLUSIONS:

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.

• Authors: Wei Hong, Baochai Lin, Beibei Zhang, Weimin Mao, Yiping Zhang
• Journal: Zhongguo fei ai za zhi = Chinese journal of lung cancer (Zhongguo Fei Ai Za Zhi) Vol. 17 Issue 4 Pg. 321-6 (Apr 2014) ISSN: 1999-6187 [Electronic] China
• PMID: 24758907 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromogranins
• Protein Kinase Inhibitors
• Quinazolines
• Erlotinib Hydrochloride
• ErbB Receptors
• GNAS protein, human
• GTP-Binding Protein alpha Subunits, Gs
• Gefitinib

Topics

• Adult
• Aged
• Carcinoma, Non-Small-Cell Lung (drug therapy, enzymology, genetics)
• Chromogranins
• ErbB Receptors (antagonists & inhibitors, genetics, metabolism)
• Erlotinib Hydrochloride
• Female
• GTP-Binding Protein alpha Subunits, Gs (genetics, metabolism)
• Gefitinib
• Humans
• Lung Neoplasms (drug therapy, enzymology, genetics)
• Male
• Middle Aged
• Mutation
• Polymorphism, Single Nucleotide
• Protein Kinase Inhibitors (administration & dosage)
• Quinazolines (administration & dosage)
• Treatment Outcome