中国临床药理学与治疗学Issue(7)：802-808,7.DOI:10.12092/j.issn.1009-2501.2018.07.013
KDR基因遗传变异对贝伐珠单抗一线治疗晚期非小细胞肺癌患者临床疗效的影响
Influence of genetic variation of KDR on clinical outcomes of advanced NSCLC treated by first line bevacizumab regimens
摘要
Abstract
AIM:To investigate the association between KDR gene polymorphism and the efficacy of bevacizumab in patients with advanced non-small cell lung cancer.METHODS:A total of 135 patients with advanced non-small cell lung cancer who were treated by bevacizumab based first line regimens were included in this study.Peripheral blood and the biopsy tissue specimens of the NSCLC patients were collected for the genotyping of genetic variation and KDR gene expression, respectively.The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis was adjusted by Cox regression analysis.RESULTS:Among the polymorphisms analyzed, only V297 I was of clinical significance.Located in the coding region, the prevalence rates of V297 I in KDR among the study population were as follows:CC genotype 99 cases (73.33％), CT genotype 33 cases (24.44％), TT genotype 3 cases (2.23％), and minor allele frequency of V297 I was0.14.The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P =0.898).TT and CT genotype patients were merged in the comparison of clinical outcomes.The analysis of patients with different genotypes found that the overall response rate (ORR) of CT/TT genotypes were 41.67％ and 47.67％ (P = 0.549), respectively.And the median progression free survival (m PFS) of patients with CT/TT genotype and CC genotype were 6.2 and 8.6 months, respectively, which was statistically significant (P = 0.003).In terms of overall survival (OS), the median overall survival (m OS) of the two genotypes were 18.9 and21.5 (P = 0.017), respectively.Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS (HR =1.95, P = 0.019).Additionally, among the 68 biopsy tissue specimens, gene expression analysis was conducted.And the results showed that the expression of KDR in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the CC genotype patients (P ＜ 0.01).CONCLUSION:Among non-small cell lung cancer patients treated by bevacizumab, the polymorphism V297 I of KDR may impact the clinical outcomes of first line bevacizumab treatment by influencing the m RNA expression of KDR.关键词
非小细胞肺癌/贝伐珠单抗/激酶插入区受体/多态性/疗效Key words
non-small cell lung cancer/bevacizumab/kinase insertion region receptor/polymorphism/clinical outcomes分类
医药卫生引用本文复制引用
王海霞,刘兴安,侯继院,龚哲,单国用..KDR基因遗传变异对贝伐珠单抗一线治疗晚期非小细胞肺癌患者临床疗效的影响[J].中国临床药理学与治疗学,2018,(7):802-808,7.基金项目
河南省郑州市科技计划项目(0910SGYS33377-1) （0910SGYS33377-1）
