Chen Xueqin, Chen Dadong, Yang Shaoyu, Ma Ruobing, Pan Yuelong, Li Xin, Ma Shenglin
Department of Medical Oncology, Nanjing Medical University, Affiliated Hangzhou Hospital(Hangzhou First People's Hospital), 261 Huansha Road, Hangzhou, Zhejiang Province 310006 China.
Cancer Cell Int. 2015 Apr 19;15:43. doi: 10.1186/s12935-015-0191-3. eCollection 2015.
The primary purpose of this study was to investigate the correlation between single nucleotide polymorphisms (SNPs) of ATP binding cassette superfamily G member 2 (ABCG2) and outcome of tyrosine kinase inhibitions (TKIs) therapy in Chinese advanced non-small-cell lung cancer (NSCLC) patients. The secondary objective was to identify biomarkers to evaluate the response to treatment and outcome of the targeted therapy.
SNP genotyping (34 G/A, 421 C/A, 1143 C/T and -15622 C/T) of ABCG2 gene in 100 patients was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The clinical characteristics of 100 patients were collected. A total of 70 patients were treated with TKIs (gefitinib, erlotinib and icotinib). The association between ABCG2 polymorphisms and clinical characteristics was evaluated. Kaplan-Meier survival curves were plotted for overall survival (OS) and analyzed with the log-rank test.
The three polymorphisms of the ABCG2 34 G/A, 421 C/A and 1143 C/T occurred more frequently compared with -15622 C/T in Chinese advanced NSCLC patients. There was no association between ABCG2 polymorphisms and clinical characteristics (p > 0.05). The median OS of patients with GG genotype at position 34 of the ABCG2 gene was significantly shorter than those with GA or AA genotype (p < 0.05). No significant difference of OS was found in 421 C/A and 1143 C/T polymorphisms (p > 0.05).
ABCG2 34 G/A may be a possible predictor of the clinical outcome of TKIs therapy in NSCLC patients.
本研究的主要目的是调查中国晚期非小细胞肺癌（NSCLC）患者中ATP结合盒超家族G成员2（ABCG2）单核苷酸多态性（SNP）与酪氨酸激酶抑制剂（TKI）治疗结果之间的相关性。次要目的是确定评估靶向治疗反应和结果的生物标志物。
使用基质辅助激光解吸/电离飞行时间质谱法对100例患者的ABCG2基因进行SNP基因分型（34 G/A、421 C/A、1143 C/T和-15622 C/T）。收集100例患者的临床特征。共有70例患者接受TKI（吉非替尼、厄洛替尼和埃克替尼）治疗。评估ABCG2多态性与临床特征之间的关联。绘制总生存期（OS）的Kaplan-Meier生存曲线并进行对数秩检验分析。
在中国晚期NSCLC患者中，ABCG2的34 G/A、421 C/A和1143 C/T这三种多态性的发生频率高于-15622 C/T。ABCG2多态性与临床特征之间无关联（p＞0.05）。ABCG2基因34位点GG基因型患者的中位OS显著短于GA或AA基因型患者（p＜0.05）。在421 C/A和1143 C/T多态性中未发现OS有显著差异（p＞0.05）。
ABCG2 34 G/A可能是NSCLC患者TKI治疗临床结果的一个潜在预测指标。
