VEGFR2基因rs10013228多态性对R0切除结直肠癌患者预后的影响

摘要/Abstract

摘要： 目的探讨血管内皮生长因子受体2（VEGFR2）基因rs10013228位点多态性与R0切除结直肠癌患者预后的关系。方法收集2010年1月至2015年12月接受R0手术切除的154例结直肠癌患者的外周血及术后93例结直肠癌组织标本，采用Tagman探针PCR基因分型技术对VEGFR2基因rs10013228位点进行基因分型，采用实时定量PCR（QPCR）检测组织中VEGFR2 mRNA水平，分析rs10013228基因型分布与临床病理特征（年龄、性别、肿瘤部位、分化程度、病理分期和辅助化疗）及VEGFR2 mRNA水平的关系，根据随访数据分析rs10013228不同基因型的预后情况，采用 Cox 风险比例模型分析影响结直肠癌预后的因素。结果全组154例患者外周血中共有VEGFR2基因rs10013228 AA型95例（61.69％）、AG型51例（33.12％）和GG型8例（5.19％），最小等位基因频率为0.22。不同基因型分布与年龄、性别、肿瘤部位、分化程度、病理分期和辅助化疗均无关（P＞0.05）。154例结直肠癌患者的中位总生存期（OS）为4.90年。单因素分析显示性别和肿瘤部位与OS无关，而年龄、分化程度、病理分期、辅助化疗和rs10013228基因型与OS有关，其中rs10013228 AG/GG型的中位OS为5.60年，长于AA型的4.40年（P＜0.05）。多因素分析显示，年龄、病理分期及rs10013228基因型为影响结直肠癌患者预后的独立因素。QPCR检测发现结直肠癌组织中rs10013228 AA型的VEGFR2 mRNA水平高于AG、GG型（4.26±1.21 vs. 2.94±0.88），差异有统计学意义（P＜0.05）。结论结直肠癌患者中VEGFR2 rs10013228与VEGFR2表达和预后有关，其中携带突变等位基因者的VEGFR2表达降低且预后较好，该位点可能是通过影响VEGFR2表达来影响预后。

关键词: 结直肠癌, 血管内皮生长因子受体2, 基因多态性, 预后

Abstract: Objective To investigate the effect of rs10013228 polymorphism of vascular endothelial growth factor receptor 2 （VEGFR2） gene on the prognosis of patients with colorectal cancer after R0 resection. Methods From January 2010 to December 2015， 154 cases of peripheral blood samples and 93 cases of postoperative cancer tissue specimens were collected from 154 patients with colorectal cancer who underwent R0 resection. Genotyping of VEGFR2 gene rs10013228 locus was performed by Tagman probe PCR genotyping. Real-time quantitative PCR （QPCR） was used to detect the level of VEGFR2 mRNA in tissues. The relationships between the distribution of rs10013228 genotype and clinicopathological parameters （age， sex， tumor location， differentiation， pathological stage and adjuvant chemotherapy） as well as the level of VEGFR2 mRNA were analyzed. The prognosis of different genotypes of rs10013228 was analyzed according to the follow-up data， and the multifactor analysis was carried out by the Cox risk proportion model. Results Among all 154 patients， there were 95 cases of rs10013228 AA gene type（61.69％）， 51 cases of AG gene type（33.12％） and 8 cases of GG gene type （5.19％） with the minimum allele frequency of 0.22. The distribution of different genotypes was not related to age， sex， tumor location， differentiation， pathological stage and adjuvant chemotherapy （P＞0.05）. The median survival time （OS） of 154 colorectal cancer patients was 4.90 years. Single factor analysis showed that sex and tumor site were not related to OS， but age， degree of differentiation， pathological stage， adjuvant chemotherapy and rs10013228 gene type were related to OS. The median OS of rs10013228 AG/GG gene type was 5.60 years， longer than that of AA type （P＜0.05）. Multivariate analysis showed that age， pathological stage and rs10013228 were independent prognostic factors for colorectal cancer patients. QPCR detection showed that VEGFR2 mRNA level of AA type was higher than that of AG/GG （4.26±1.21 vs. 2.94±0.88）， and the difference was statistically significant （P＜0.05）. Conclusion The VEGFR2 rs10013228 in colorectal cancer patients is related to the expression of VEGFR2 and the prognosis. Patients carrying the mutant allele of VEGFR2 present a lower expression of VEGFR2 and a better prognosis. It may affect the prognosis by influencing the expression of VEGFR2.

Key words: Colorectal cancer, Vascular endothelial growth factor receptor 2（VEGFR2）, Polymorphism, Prognosis

中图分类号:

R735.3

张德志, 张宇, 朱少功. VEGFR2基因rs10013228多态性对R0切除结直肠癌患者预后的影响[J]. 临床肿瘤学杂志, 2018, 23(5): 424-428.

ZHANG Dezhi, ZHANG Yu, ZHU Shaogong.. Effect of rs10013228 polymorphism of VEGFR2 gene on prognosis of patients with R0 resection of colorectal cancer[J]. Chinese Clinical Oncology, 2018, 23(5): 424-428.

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