Association between genetic variation of kinase insert domain receptor and prognosis in colorectal cancer patients received 5-FU based adjuvant chemotherapy
10.3872/j.issn.1007-385x.2019.03.011
- VernacularTitle: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
- Author:
LI Xiaojie
1
,
2
;
ZHANG Shengwei
1
,
2
;
WANG Huasheng
1
,
2
;
WANG Dong
1
,
2
;
MEI Jiazhuan
2
,
3
;
DENG Yewei
1
,
2
Author Information
1. Department of anus and intestine surgery, People&rsquo
2. s Hospital of Zhengzhou
3. Department of oncology, People&rsquo
- Publication Type:Journal Article
- Keywords:
colorectal cancer(CRC);
kinase insert domain receptor(KDR);
rs2071559;
genetic variation;
5-fluorouracil;
prognosis
- From:
Chinese Journal of Cancer Biotherapy
2019;26(3):317-322
- CountryChina
- Language:Chinese
-
Abstract:
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 mRNAin 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 associated with clinical outcomes in patients with colorectal cancer. KDR rs2071559 may affect the prognosis of colorectal cancer patients by affecting the mRNAexpression of KDR.
- Full text:20190311.pdf
