Influence of KDR Genetic Variation on the Efficacy and Safety of Patients with Chemotherapy Refractory Metastatic CRC Who Received Apatinib Treatment.
Influence of KDR Genetic Variation on the Efficacy and Safety of Patients with Chemotherapy Refractory Metastatic CRC Who Received Apatinib Treatment.
复制标题
KDR基因变异对化疗难治性转移性CRC患者接受阿帕替尼治疗的疗效和安全性的影响
DOI：
10.2147/ijgm.s300968
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发表时间：
2021
影响因子：
2.3
通讯作者：
Ba Y
中科院分区：
文献类型：
--
作者：
Bai M;Li ZG;Ba Y
本研究的目的是研究激酶插入结构域受体（KDR）遗传变异对接受阿帕替尼治疗的化疗难治性转移性结直肠癌（CRC）患者的疗效和安全性的影响。方法回顾性分析108例接受阿帕替尼治疗的化疗难治性转移性结直肠癌患者的临床资料。对患者的治疗效果进行评价。分别进行预后和记录安全性特征。分别采集患者外周血标本和外周血单个核细胞（PBMC）进行遗传变异分析和KDR基因mRNA表达分析。基因型状态和临床结果之间的关联。结果108例接受阿帕替尼治疗的转移性结直肠癌患者的客观缓解率（ORR）和疾病控制率（DCR）分别为5.6%和69.4%。生存分析结果显示，108例转移性结直肠癌患者的中位无进展生存期（PFS）和总生存期（OS）分别为3.6个月（95%CI：3.03-4.17个月）和8.9个月（95%CI：7.57-10.23个月）。随后对KDR基因的遗传变异进行了分析，结果表明rs 2071559具有临床意义。rs 2071559的次要等位基因频率为0.22，基因型分布符合Hardy-Weinberg平衡（P=0.949）。通过显性遗传方式对TC和CC基因型患者的预后分析显示，TT基因型和TC/CC基因型患者的中位PFS分别为4.1和3.0个月（P=0.012）。此外，两种基因型患者的中位OS分别为10.5和6.1个月（P=0.007）。多因素考克斯回归分析显示TC/CC基因型是影响总生存率的独立因素（HR =0.65，P=0.021）。mRNA表达分析显示，rs 2071559基因型不同的PBMC中KDR mRNA的表达差异有统计学意义（P<0.001）。结论阿帕替尼治疗化疗难治性转移性结直肠癌具有潜在的上级临床疗效。KDR多态性rs 2071559可作为评估接受阿帕替尼治疗的CRC患者预后的潜在生物标志物。
Background The aim of the present study was to investigate the influence of kinase insert domain containing receptor (KDR) genetic variation on the efficacy of treatment and safety of patients with chemotherapy-refractory metastatic colorectal cancer (CRC) receiving apatinib. Methods A total of 108 patients with chemotherapy refractory metastatic CRC who were treated with apatinib participated in this study retrospectively. Efficacy of the patients’ treatment was evaluated. Prognosis was carried out and safety profile was documented, respectively. Blood specimens and peripheral blood mononuclear cells (PBMC) of the patients were obtained for the analysis of genetic variation and KDR gene mRNA expression, respectively. The association between genotype status and clinical outcomes was presented. Results Objective response rate (ORR) and disease control rate (DCR) of the 108 patients with metastatic CRC receiving apatinib treatment were 5.6% and 69.4%, respectively. Survival analysis results exhibited that the median progression-free survival (PFS) and overall survival (OS) of the 108 patients with metastatic CRC was 3.6 months (95% confidence interval (CI): 3.03–4.17 months) and 8.9 months (95% CI: 7.57–10.23 months), respectively. Subsequently, the analysis of KDR genetic variation indicated that rs2071559 was of clinical significance. The minor allele frequency of rs2071559 was 0.22 and the genotype status corresponded with Hardy-Weinberg equilibrium (P=0.949). Prognosis analysis in a dominant inheritance manner through the combination of patients with TC and CC genotype showed that the median PFS of patients with TT genotype and TC/CC genotype was 4.1 and 3.0 months, respectively (P=0.012). Furthermore, the median OS of patients with the two genotypes was 10.5 and 6.1 months, respectively (P=0.007). Additionally, multivariate Cox regression analysis of OS showed that TC/CC genotype was an independent factor for OS (Hazard ratio (HR)=0.65, P=0.021). Interestingly, mRNA expression analysis suggested that the mRNA expression of KDR in PBMC differed significantly according to rs2071559 genotype status (P<0.001). Conclusion Apatinib demonstrated a potentially superior clinical outcome for patients with chemotherapy-refractory metastatic CRC. KDR polymorphism rs2071559 could be used as a potential biomarker for the prognosis evaluation of patients with CRC receiving apatinib therapy.