Fan H J, Yuan J, Wu J J, Jia Y X, Ma Y H, Li X Y
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Yi Xue Za Zhi. 2019 Jan 8;99(2):99-104. doi: 10.3760/cma.j.issn.0376-2491.2019.02.005.
To investigate the influence of polymorphisms of vascular endothelial growth factor receptor-2(VEGFR2) on clinical outcomes and safety of advanced non-small-cell lung cancer (NSCLC) treated by first line Bevacizumab plus chemotherapy regimens. A total of 148 patients with advanced NSCLC who were treated by bevacizumab based first line regimens from January 2013 to January 2017 in the Department of Oncology of the First Affiliated Hospital of Zhengzhou University 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 VEGFR2 mRNA expression, respectively. The association between genotype and other characteristics and VEGFR2 mRNA expression were analyzed. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis were adjusted by Cox regression analysis. Of the polymorphisms analyzed, only 889C>T was of clinical significance. Located in the coding region, the prevalence of 889C>T in VEGFR2 among the study population were as follows: CC genotype 108 cases (72.97%), CT genotype 36 cases (24.32%), TT genotype 4 cases (2.71%), minor allele frequency of 889C>T was 0.15. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (0.636). TT and CT genotype patients were merged in the comparison of clinical outcomes. The analysis of patients with different genotypes found that the objective response rates (ORR) of CT/TT genotypes and CC genotypes were 40.00% and 48.15% (0.377), respectively. And the median progression free survival (mPFS) of patients with CT/TT genotype and CC genotype were 6.1 and 8.7 months, respectively, which was statistically significant (0.002). In terms of overall survival (OS), the median overall survival (mOS) of the two genotypes were 18.7 and 21.4 months (0.012), respectively. Adjusted in multivariate analysis, 889C>T were an independent factor for progression free survival (1.96, 0.014). No association between the 889C>T and adverse reactions was found in the safety analysis. Of the 69 biopsy tissue specimens, gene expression analysis showed that the mRNA expression of VEGFR2 in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the CC genotype patients (0.001). The polymorphism 889C>T of VEGFR2 may have worse influence on clinical outcomes of advanced NSCLC treated by first line bevacizumab plus chemotherapy regimens, while no significant impact on safety.
探讨血管内皮生长因子受体2（VEGFR2）基因多态性对一线贝伐单抗联合化疗方案治疗晚期非小细胞肺癌（NSCLC）临床疗效及安全性的影响。本研究纳入了2013年1月至2017年1月在郑州大学第一附属医院肿瘤科接受以贝伐单抗为基础的一线方案治疗的148例晚期NSCLC患者。分别收集NSCLC患者的外周血和活检组织标本，用于基因变异基因分型和VEGFR2 mRNA表达检测。分析基因型与其他特征及VEGFR2 mRNA表达之间的关联。采用Kaplan-Meier生存分析对基因型与预后进行单因素分析，采用Cox回归分析进行多因素分析。在所分析的多态性中，只有889C>T具有临床意义。位于编码区，研究人群中VEGFR2基因889C>T的患病率如下：CC基因型108例（72.97%），CT基因型36例（24.32%），TT基因型4例（2.71%），889C>T的次要等位基因频率为0.15。三种基因型的分布符合Hardy-Weinberg平衡（0.636）。在临床疗效比较中，将TT和CT基因型患者合并。对不同基因型患者的分析发现，CT/TT基因型和CC基因型患者的客观缓解率（ORR）分别为40.00%和48.15%（0.377）。CT/TT基因型和CC基因型患者的中位无进展生存期（mPFS）分别为6.1个月和8.7个月，差异有统计学意义（0.002）。在总生存期（OS）方面，两种基因型的中位总生存期（mOS）分别为18.7个月和21.4个月（0.012）。多因素分析校正后，889C>T是无进展生存期的独立因素（1.96，0.014）。安全性分析未发现889C>T与不良反应之间存在关联。在69例活检组织标本中，基因表达分析显示，CT/TT基因型患者癌组织中VEGFR2的mRNA表达显著高于CC基因型患者（0.001）。VEGFR2基因多态性889C>T可能对一线贝伐单抗联合化疗方案治疗晚期NSCLC的临床疗效有更差的影响，而对安全性无显著影响。
