[摘要] 目的：探讨血管内皮生长因子受体2（VEGFR2）基因V297I 位点对贝伐珠单抗联合化疗治疗晚期非小细胞肺癌（nonsmallcell lung cancer，NSCLC）患者疗效的影响。方法：收集2010 年1 月到2017 年1 月在河南中医药大学第三附属医院肿瘤科135 例一线接受贝伐珠单抗联合含铂双药化疗的晚期NSCLC患者的临床资料，用PCR-RFLP 法检测患者外周血VEGFR2 基因型，qPCR法检测患者癌组织中VEGFR2 mRNA的表达。通过Logistic 回归模型分析多态性位点的基因型和其他变量的相关性，用Kaplan-Meier 法分析基因型和预后的相关性，以Cox风险模型分析患者PFS的危险因素。结果：在VEGFR2 的多态性位点中，只发现了V297I 位点其有临床意义。V297I 位点位于该基因的编码区，在研究人群的基因分布频率为CC型99 例（73.33%）、CT型33 例（24.44%）、TT 型3 例（2.23%），最小等位基因频率为0.14，3 种基因型分布频率符合哈迪温-伯格平衡（P>0.05）。135 例NSCLC 患者的ORR 为45.93%，中位PFS 为8.2 个月，中位OS 为20.8 个月。CT/TT 型和CC 型患者的ORR 分别为41.67%和47.47%（P>0.05），中位PFS 分别为6.2 和8.6 个月（P<0.01），中位OS分别为18.9 和21.5 个月（P<0.05）。CT/TT基因型患者癌组织中VEGFR2 mRNA水平明显高于CC 型患者（P<0.01）。影响NSCLC 患者PFS 的危险因素有：V297I 位点和性别、ECOG评分。结论：在接受贝伐珠单抗联合化疗治疗的晚期NSCLC患者中，VEGFR2 基因V297I 位点可能通过VEGFR2 基因的表达影响贝伐珠单抗一线治疗NSCLC患者的疗效和预后。

[Abstract] Objective: To investigate the effect of VEGFR2 gene polymorphism V297I on the clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with bevacizumab combining with chemotherapy. Methods: A total of 135 patients with advanced NSCLC, who were treated by bevacizumab plus platinum-based chemotherapy for first-line regimen, were included in this study. PCR-RFLP assay was used to detect the VEGFR2 genotypes in peripheral blood of patients and qPCR was used to detect the VEGFR2 mRNA in the cancer tissues of NSCLC patients. Logistic regression analysis was used to analyze the correlation between gene polymorphism and other variants, Kaplan-Meier assay to analyze the correlation between genotype and prognosis, and Cox regression model to analyze the risk factors for patients’PFS. Results: Of the polymorphisms analyzed, only polymorphism V297I was found to be of clinical significance. V297I locates in the coding region of VEGFR2, and it’s prevalence in the study population was as follows: CC genotype in 99 cases (73.33%), CT genotype in 33 cases (24.44%) and TT genotype in 3 cases (2.23%); the frequency of minor allele was 0.14, and the distribution of three genotypes was in accordance with Hardy-Weinberg equilibrium (P>0.05). The overall objective remission rate (ORR) of the 135 patients was 45.93%, the median progression free survival (mPFS) was 8.2 months and the median overall survival (mOS) was 20.8 months. The ORR, mPFS and mOS of patients with CT/TT genotype and CC genotype were 41.67%, 6.2 months, 18.9 months and 47.47%, 8.9 months and 21.5 months, respectively (all P<0.05). Additionally, the mRNA expression of VEGFR2 in cancer tissues of the patients with CT/TT genotype was significantly higher than those with CC genotype (P<0.01). The risk factors for patients’PFS included V297I, gender and ECOG score. Conclusion: Among advanced NSCLC patients treated by bevacizumab plus platinum-based chemotherapy, the polymorphism V297I of VEGFR2 may impact the clinical outcomes and prognosis of NSCLC patients treated with bevacizumab first line treatment by influencing the mRNA expression of VEGFR2.

河南省郑州市科技发展计划项目（No. 20150061）