Implication of KDR Polymorphism rs2071559 on Therapeutic Outcomes and Safety of Postoperative Patients with Gastric Cancer Who Received S-1-Based Adjuvant Chemotherapy: A Real-World Exploratory Study.

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Pharmacogenomics & Personalized Medicine Pub Date : 2023-11-28 eCollection Date: 2023-01-01 DOI:10.2147/PGPM.S432528
Lei Meng, Jun Cao, Li Kang, Gang Xu, Da-Wei Yuan, Kang Li, Kun Zhu
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引用次数: 0

Abstract

Objective: Regimens of S-1-based adjuvant chemotherapy are of great significance in attenuating recurrence risk in postoperative patients with gastric cancer (GC). Kinase insert-domain receptor (KDR) gene plays an essential role in tumor growth and metastasis. This study aimed to investigate the implication of KDR genotyping on the therapeutic outcomes of patients with gastric cancer (GC) who received S-1-based adjuvant chemotherapy.

Methods: A total of 169 postoperative GC with pathological staging of II and III and no metastasis who received S-1-based adjuvant chemotherapy were included retrospectively. Peripheral blood specimens were collected and prepared for KDR genotyping and KDR mRNA expression. Correlation between KDR genotype status and prognosis was performed using Kaplan-Meier survival analysis, and multivariate analysis was ultimately adopted using Cox regression analysis.

Results: Median disease-free survival (DFS) of the 169 patients with GC was 5.1 years [95% confidence interval (CI): 4.25-5.95] and median overall survival (OS) was 6.7 years (95% CI: 5.44-7.96). Rs2071559 was located at the upstream region, and the prevalence among 169 patients with GC was as follows: AA genotype in 104 cases (61.5%), AG genotype in 57 cases (33.7%), and GG genotype in 8 cases (4.7%), yielding a minor allele frequency of 0.22, which was consistent with Hardy-Weinberg equilibrium (P=0.958). Median DFS of patients with AA and AG/GG genotypes was 6.0 years and 4.0 years, respectively (P=0.002). Additionally, patients with the AA genotype had longer OS than those with the AG/GG genotype [median OS: not reached (NR) vs 5.5 years, P=0.011]. Additionally, KDR mRNA expression was significantly higher in patients with the AG/GG genotype than that in those with the AA genotype (P<0.001).

Conclusion: Rs2071559 in KDR gene might be a promising biomarker for evaluating the recurrence risk and OS of patients with GC who received S-1-based adjuvant chemotherapy. This conclusion should be confirmed in randomized clinical trials.

KDR多态性rs2071559对胃癌术后患者接受s -1辅助化疗的治疗结果和安全性的影响:一项真实世界的探索性研究
目的:以s -1为基础的辅助化疗方案对降低胃癌术后患者复发风险具有重要意义。激酶插入结构域受体(Kinase insert-domain receptor, KDR)基因在肿瘤的生长和转移中起重要作用。本研究旨在探讨KDR基因分型对胃癌(GC)患者接受s -1辅助化疗治疗结果的影响。方法:回顾性分析169例病理分期为ⅱ、ⅲ期、无转移的胃癌术后行s -1辅助化疗的病例。采集外周血标本进行KDR基因分型和KDR mRNA表达检测。KDR基因型状态与预后的相关性采用Kaplan-Meier生存分析,最终采用Cox回归分析进行多因素分析。结果:169例胃癌患者的中位无病生存期(DFS)为5.1年[95%可信区间(CI): 4.25-5.95],中位总生存期(OS)为6.7年(95% CI: 5.44-7.96)。Rs2071559位于上游区域,169例GC患者中AA基因型104例(61.5%),AG基因型57例(33.7%),GG基因型8例(4.7%),等位基因频率较小,为0.22,符合Hardy-Weinberg平衡(P=0.958)。AA和AG/GG基因型患者的中位DFS分别为6.0年和4.0年(P=0.002)。此外,AA基因型患者的生存期比AG/GG基因型患者更长[中位生存期:未达到(NR) vs 5.5年,P=0.011]。此外,AG/GG基因型患者的KDR mRNA表达量显著高于AA基因型患者(p结论:KDR基因的Rs2071559可能是评估GC患者接受s -1辅助化疗复发风险和OS的有希望的生物标志物。这一结论有待随机临床试验的证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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