Liu Di, Xu Wen, Zhang Zhi-Wei, Qian Ji, Zheng Hui, Zhang Jie, Su Bo
Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China E-mail :
Asian Pac J Cancer Prev. 2015;16(2):775-81. doi: 10.7314/apjcp.2015.16.2.775.
RB1 (retinoblastoma 1) was reportedly one of the major determinative factors for sensitivity to taxanes in previous studies. In this study, we investigated the influence of RB1 single nucleotide polymorphisms (SNPs) on the efficacy of platinum-taxane regimens in advanced NSCLC patients.
234 cases of patients with advanced NSCLC who were treated with first-line platinum-taxane agents were enrolled in this study. Genomic DNA was extracted from patients' peripheral blood samples using a QIAamp DNA Maxi Kit, and genotyped by iSelect HD Bead-Chip.
Regression analyses were conducted through the univariate and multivariate Cox proportional hazards model in the 234 patients. The results showed that of the eight RB1 tagSNPs, only rs4151510 was a positive predictive factor for the advanced NSCLC patients treated with platinum taxanes regimen. The patients with G/G genotype of RB rs4151510 had longer overall survival (OS) than the non-G/G genotype (p=0.018). The histology was also correlated with OS in the whole advanced NSCLC patients. Three tagSNPs of RB1, rs4151510, rs4151465, rs9568036 were significantly associated with OS in the advanced NSCLC patients with squamous cell histology using Kaplan-Meier overall survival analysis stratified by histology.
RB1 genomic variants were correlated with the efficacy of platinum-taxanes regimen. RB rs4151510 is an independent factor of the prognosis of NSCLC patients receiving platinum-taxane chemotherapy.
据报道,RB1(视网膜母细胞瘤1)是先前研究中对紫杉烷敏感性的主要决定因素之一。在本研究中,我们调查了RB1单核苷酸多态性(SNP)对晚期非小细胞肺癌(NSCLC)患者铂类-紫杉烷方案疗效的影响。
本研究纳入了234例接受一线铂类-紫杉烷药物治疗的晚期NSCLC患者。使用QIAamp DNA Maxi试剂盒从患者外周血样本中提取基因组DNA,并通过iSelect HD Bead-Chip进行基因分型。
对234例患者通过单因素和多因素Cox比例风险模型进行回归分析。结果显示,在8个RB1标签SNP中,只有rs4151510是接受铂类-紫杉烷方案治疗的晚期NSCLC患者的阳性预测因子。RB rs4151510的G/G基因型患者的总生存期(OS)长于非G/G基因型患者(p = 0.018)。在整个晚期NSCLC患者中,组织学类型也与OS相关。使用按组织学分层的Kaplan-Meier总生存分析,RB1的3个标签SNP,rs4151510、rs4151465、rs9568036与鳞状细胞组织学类型的晚期NSCLC患者的OS显著相关。
RB1基因变异与铂类-紫杉烷方案的疗效相关。RB rs4151510是接受铂类-紫杉烷化疗的NSCLC患者预后的独立因素。