Hong Wei, Lin Baochai, Zhang Beibei, Mao Weimin, Zhang Yiping
Zhejiang Cancer Hospital, Zhejiang Key Laboratory of the Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou 310022, China.
Department of Medical Oncology, the First Affiliated Hospital of WenZhou Medical College, Wenzhou 325000, China.
Zhongguo Fei Ai Za Zhi. 2014 Apr;17(4):321-6. doi: 10.3779/j.issn.1009-3419.2014.04.06.
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.
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.
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).
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.
表皮生长因子受体（EGFR）激活突变预示着对EGFR酪氨酸激酶抑制剂（TKIs）有良好反应。然而，肺癌患者的EGFR突变状态往往未知，因为可供检测的肿瘤标本很少。TKIs诱导肿瘤细胞凋亡，这与多个凋亡相关基因有关。本研究旨在探讨GNAS1 T393C多态性与EGFR突变状态未知的经治晚期非小细胞肺癌（NSCLC）患者TKI治疗疗效之间的关系。
从浙江省肿瘤医院招募了116例患者进行研究，所有患者在先前化疗失败后均接受吉非替尼或厄洛替尼治疗。我们通过聚合酶链反应（PCR）检测患者外周血淋巴细胞中GNAS1 T393C多态性的基因型。采用SPSS 18.0版进行统计分析。
总缓解率为29.3%。未发现GNAS1 T393C多态性与客观缓解率之间存在显著关联。GNAS1 T393C CC基因型患者的疾病控制率低于变异基因型（TT或CT）患者（46.2%对73.8%，P = 0.039）。单因素分析确定性别、吸烟史、组织学类型和GNAS1 T393C多态性为无进展生存期（PFS）的预测标志物（P = 0.04，P < 0.001，P < 0.001和P = 0.005）。对包括吸烟史、体能状态评分、组织学类型、GNAS1 T393C多态性在内的因素进行多因素分析表明，GNAS1 T393C多态性与PFS独立相关（P = 0.007）。
我们的数据表明，在接受酪氨酸激酶抑制剂治疗的晚期NSCLC患者中，GNAS1 T393C CC基因型是疾病控制率和无进展生存期的不良预测标志物。
