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[The impact of genetic variation of KDR on clinical outcomes of advanced colorectal cancer patients treated by first line bevacizumab based regimens].

作者信息

Wang H X, Mei X, Gong T X, Han N, Liu P, Wang J, Zhang Z M

机构信息

Department of Oncology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2018 Sep 11;98(34):2737-2742. doi: 10.3760/cma.j.issn.0376-2491.2018.34.012.


DOI:10.3760/cma.j.issn.0376-2491.2018.34.012
PMID:30220171
Abstract

To investigate the association between kinase insertion region receptor (KDR) gene genetic variation and the efficacy of bevacizumab in patients with advanced colorectal cancer(CRC) were investigated in this study. 118 patients with advanced colorectal cancer who were treated by bevacizumab based first line regimens were included in this study. Peripheral blood and the biopsy tissue specimens of the CRC patients were collected for the genotyping of genetic variation and KDR gene expression, respectively. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate were adjusted by Cox regression analysis. Located in the coding region, the prevalence of 889 C>T in KDR among the study population were as follows: CC genotype 86 cases (72.88%), CT genotype 30 cases (25.42%), TT genotype 2 cases (1.70%), minor allele frequency of 889 C>T is 0.14. The distribution of three genotypes in accordance with Hardy-Weinberg Equilibrium (=0.737). There were no statistical differences in the distribution of the genotypes in baseline clinical data. TT and CT genotype patients were merged in the comparison of clinical outcomes. The clinical outcomes analysis of patients with different genotypes found that the objective response rates (ORR) of CT/TT genotypes were 34.38% and 43.02% (=0.395), respectively. And the median progression free survival (PFS) of patients with CT/TT genotype and CC genotype were 7.5 and 9.7 months respectively, which was statistically significant (=0.009). In terms of overall survival (OS), the median OS of the two genotypes were 19.3 and 20.1 (=0.025), respectively. Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS (=1.88, =0.023). Additionally, of the 57 biopsy tissue specimens, gene expression analysis was conducted. And the results showed that the expression of KDR in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the CC genotype patients (<0.001). Among advanced colorectal cancer patients treated by bevacizumab, the polymorphism 889 C>T of KDR may impact the clinical outcomes of bevacizumab first line treatment by influencing the mRNA expression of KDR.

摘要

相似文献

[1]
[The impact of genetic variation of KDR on clinical outcomes of advanced colorectal cancer patients treated by first line bevacizumab based regimens].

Zhonghua Yi Xue Za Zhi. 2018-9-11

[2]
[Influence of polymorphisms of VEGFR2 on clinical outcomes and safety of advanced non-small-cell lung cancer treated by first line Bevacizumab plus chemotherapy regimens].

Zhonghua Yi Xue Za Zhi. 2019-1-8

[3]
The Influence of KDR Genetic Variation on the Efficacy and Safety of Patients With Advanced NSCLC Receiving First-Line Bevacizumab Plus Chemotherapy Regimen.

Technol Cancer Res Treat. 2021

[4]
[Influence of apatinib and VEGFR2-906T>C polymorphism on clinical outcomes of advanced non-small cell lung cancer patients].

Zhonghua Yi Xue Za Zhi. 2019-1-8

[5]
[The influence of Thymidine Phosphorylase genetic variation on clinical outcomes and safety of colorectal cancer patients received adjuvant chemotherapy after R0 resection].

Zhonghua Yi Xue Za Zhi. 2018-8-28

[6]
Influence of KDR Genetic Variation on the Effectiveness and Safety of Bevacizumab in the First-Line Treatment for Patients with Advanced Colorectal Cancer.

Int J Gen Med. 2022-6-16

[7]
Influence of VEGFR2 gene polymorphism on the clinical outcomes of apatinib for patients with chemotherapy-refractory extensive-stage SCLC: a real-world retrospective study.

Int J Clin Oncol. 2021-4

[8]
Influence of KDR Genetic Variation on the Efficacy and Safety of Patients with Chemotherapy Refractory Metastatic CRC Who Received Apatinib Treatment.

Int J Gen Med. 2021-3-25

[9]
Clinical Outcomes and Safety of Apatinib Mesylate in the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer in Patients Who Progressed After Standard Therapy and Analysis of the Gene Polymorphism.

Onco Targets Ther. 2020-1-21

[10]
[Clinical outcomes of gastric cancer patients received capecitabine based adjuvant chemotherapy and the corresponding pharmacogenomics analysis].

Zhonghua Yi Xue Za Zhi. 2018-11-13

引用本文的文献

[1]
Genetic mechanism of β-alanine metabolic pathway affecting colorectal cancer prognosis.

BMC Gastroenterol. 2025-7-1

[2]
Influence of KDR Genetic Variation on the Effectiveness and Safety of Bevacizumab in the First-Line Treatment for Patients with Advanced Colorectal Cancer.

Int J Gen Med. 2022-6-16

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