Wang H X, Mei X, Gong T X, Han N, Liu P, Wang J, Zhang Z M
Department of Oncology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China.
Zhonghua Yi Xue Za Zhi. 2018 Sep 11;98(34):2737-2742. doi: 10.3760/cma.j.issn.0376-2491.2018.34.012.
To investigate the association between kinase insertion region receptor (KDR) gene genetic variation and the efficacy of bevacizumab in patients with advanced colorectal cancer(CRC) were investigated in this study. 118 patients with advanced colorectal cancer who were treated by bevacizumab based first line regimens were included in this study. Peripheral blood and the biopsy tissue specimens of the CRC 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 were adjusted by Cox regression analysis. Located in the coding region, the prevalence of 889 C>T in KDR among the study population were as follows: CC genotype 86 cases (72.88%), CT genotype 30 cases (25.42%), TT genotype 2 cases (1.70%), minor allele frequency of 889 C>T is 0.14. The distribution of three genotypes in accordance with Hardy-Weinberg Equilibrium (=0.737). There were no statistical differences in the distribution of the genotypes in baseline clinical data. TT and CT genotype patients were merged in the comparison of clinical outcomes. The clinical outcomes analysis of patients with different genotypes found that the objective response rates (ORR) of CT/TT genotypes were 34.38% and 43.02% (=0.395), respectively. And the median progression free survival (PFS) of patients with CT/TT genotype and CC genotype were 7.5 and 9.7 months respectively, which was statistically significant (=0.009). In terms of overall survival (OS), the median OS of the two genotypes were 19.3 and 20.1 (=0.025), respectively. Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS (=1.88, =0.023). Additionally, of the 57 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 (<0.001). Among advanced colorectal cancer patients treated by bevacizumab, the polymorphism 889 C>T of KDR may impact the clinical outcomes of bevacizumab first line treatment by influencing the mRNA expression of KDR.
本研究旨在探讨激酶插入区域受体（KDR）基因遗传变异与贝伐单抗治疗晚期结直肠癌（CRC）患者疗效之间的关联。本研究纳入了118例接受以贝伐单抗为基础的一线治疗方案的晚期结直肠癌患者。分别采集CRC患者的外周血和活检组织标本，用于基因变异的基因分型和KDR基因表达检测。采用Kaplan-Meier生存分析对基因型与预后进行单因素分析，多因素分析采用Cox回归分析进行校正。位于编码区，研究人群中KDR基因889 C>T的发生率如下：CC基因型86例（72.88%），CT基因型30例（25.42%），TT基因型2例（1.70%），889 C>T的次要等位基因频率为0.14。三种基因型的分布符合Hardy-Weinberg平衡（=0.737）。基线临床数据中基因型分布无统计学差异。在比较临床结局时，将TT和CT基因型患者合并。对不同基因型患者的临床结局分析发现，CT/TT基因型患者的客观缓解率（ORR）分别为34.38%和43.02%（=0.395）。CT/TT基因型和CC基因型患者的中位无进展生存期（PFS）分别为7.5个月和9.7个月，差异有统计学意义（=0.009）。在总生存期（OS）方面，两种基因型的中位OS分别为19.3个月和20.1个月（=0.025）。在PFS的多因素Cox回归分析中校正后，CT/TT基因型是PFS的独立因素（=1.88，=0.023）。此外，对57例活检组织标本进行了基因表达分析。结果显示，CT/TT基因型患者癌组织中KDR的表达明显高于CC基因型患者（<0.001）。在接受贝伐单抗治疗的晚期结直肠癌患者中，KDR基因889 C>T多态性可能通过影响KDR的mRNA表达影响贝伐单抗一线治疗的临床结局。
