KDR基因遗传变异与接受5-FU辅助化疗的结直肠癌患者预后的关系  

Association between genetic variation of kinase insert domain receptor and prognosis in colorectal cancer patients received 5-FU based adjuvant chemotherapy

作　　者：李晓洁[1] 张胜威[1] 王华胜[1] 王东[1] 梅家转[2] 邓业巍[1] LI Xiaojie;ZHANG Shengwei;WANG Huasheng;WANG Dong;MEI Jiazhuan;DENG Yewei(Department of anus and intestine surgery,People’s Hospital of Zhengzhou,Zhengzhou 450000,Henan,China;Department of oncology,People’s Hospital of Zhengzhou,Zhengzhou 450000,Henan,China)

机构地区：[1]郑州人民医院肛肠外科,河南郑州450000 [2]郑州人民医院肿瘤科,河南郑州450000

出　　处：《中国肿瘤生物治疗杂志》2019年第3期317-322,共6页Chinese Journal of Cancer Biotherapy

基　　金：河南省郑州市科技发展计划资助项目(No.20150061)~~

摘　　要：目的:探讨激酶插入区受体(kinase insert domain receptor,KDR)基因遗传变异与接受5-FU为基础辅助化疗的结直肠癌(colorectal cancer, CRC)患者预后的关系。方法:回顾性分析2012年1月至2017年12月在郑州人民医院肛肠外科接受手术切除治疗的CRC患者共176例的临床资料,并收集93例术后癌组织标本。采用聚合酶链式反应-限制性片段长度多态性(PCRRFLP)技术检测KDR基因多态性位点基因型,采用qPCR检测癌组织中KDR基因mRNA的表达水平。通过logistic回归模型分析多态性位点的基因型与其他变量的相关性,非参数检验分析KDR不同基因型的表达,采用Kaplan-Meier生存分析单变量KDR基因型与患者预后的关系,并通过Cox风险比例模型对其他变量进行校正。结果:在KDR的多态性位点中,仅发现了rs2071559位点具有临床意义。该位点在176例CRC患者中的分布频率:TT基因型95例(53.98%),TC基因型70例(39.77%),CC基因型11例(6.25%);最小等位基因频率为0.26;3种基因型分布符合Hardy-Weinberg遗传平衡定律(P=0.690)。携带C等位基因的TC/CC基因型患者与野生型TT基因型患者的中位无复发生存期(mDFS)分别为4.4和3.2年(P<0.05);TC/CC基因型和TT基因型患者的中位总生存期(mOS)分别为5.2和4.0年(P<0.05)。对OS构建多变量的Cox模型校正后,TC/CC基因型对mOS具有明显影响(OR=0.55,P<0.05)。rs2071559位点TC/CC基因型患者相对于野生型TT基因型患者KDR m RNA表达水平显著降低(P<0.01)。结论:KDR基因rs2071559位点多态性与CRC患者临床治疗效果相关,其机制是可能通过影响KDR mRNA表达水平进而影响CRC患者的预后。Objective:To investigate the association between genetic variation of kinase insert domain receptor(KDR)and the prognosis in colorectal cancer(CRC)patients received 5-FU based adjuvant chemotherapy.Methods:The clinical data of 176 CRC patients,who underwent surgical treatment at the Department of Anus and Intestine Surgery,People’s Hospital of Zhengzhou during January 2012 and December 2017,were retrospectively analyzed,and 93 cases of tumor tissues were collected for this study.The genotype of KDR polymorphism locus was detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).qPCR was used to detect the expression of KDR mRNA in colorectal cancer tissues.The correlation between the polymorphism genotypes and other variables was analyzed by logistic regression model.The expression of different genotypes of KDR was analyzed by nonparametric test.The relationship between KDR genotype and prognosis of patients was analyzed by Kaplan-Meier survival analysis,and the other variables were adjusted by Cox risk scale model.Results:Of the polymorphisms analyzed,only rs2071559 was of clinical significance.The distribution frequency of KDR rs2071559 in 176 CRC patients was as follows:TT genotype in 95 cases(53.98%),TC genotype in 70 cases(39.77%)and CC genotype in 11 cases(6.25%);the minor allele frequency was 0.26;and the distribution of three genotypes was in accordance with Hardy-Weinberg's Equilibrium(P=0.690).The median disease free survival(mDFS)of patients carrying C allele and wild type TT genotype was 4.4 and 3.2 years,respectively(P<0.05);The median overall survival(mOS)of patients with TC/CC genotype and TT genotype was 5.2 and 4.0 years,respectively(P<0.05).After COX model modification,the effect of TC/CC genotype on mOS was still statistically significant(OR=0.55,P<0.05).The mRNA expression of KDR in cancer tissues of the patients with TC/CC genotypes were significantly lower than those of the wild type TT genotype(P<0.01).Conclusion:The polymorphism of KDR rs2071559 is associat

关 键 词：结直肠癌 激酶插入区受体基因 rs2071559 遗传变异 5-氟尿嘧啶 预后 

分 类 号：R735.37[医药卫生—肿瘤] R392.2[医药卫生—临床医学]