Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S397382

Xiongjie Jia, Tao Zhang, Junjie Sun, Hengxue Lin, Tianliang Bai, Yating Qiao, Yaxin Li, Gang Li, Guicun Li, Xinyu Peng, Aimin Zhang

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引用次数: 1

Abstract

Objective: Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy.

Methods: A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test.

Results: Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (P=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (P=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (P=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype (P<0.001).

Conclusion: Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP. The conclusion of this study should be validated in prospective clinical trials subsequently.

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胸苷磷酸化酶Rs11479与结直肠癌患者卡培他滨辅助化疗预后的关系

目的:胸苷磷酸化酶(TYMP)基因在结直肠癌(CRC)发生发展过程中具有潜在意义，在卡培他滨代谢中发挥重要作用。本研究旨在确定TYMP多态性与术后接受卡培他滨辅助化疗的结直肠癌患者预后的关系。方法:回顾性分析218例行手术切除加卡培他滨辅助化疗的结直肠癌患者。采集患者外周血和外周血单个核细胞(PBMC)标本，分别对TYMP多态性和TYMP mRNA表达进行基因分型。单因素分析基因型与预后采用Kaplan-Meier生存分析，多因素分析采用Cox回归分析。采用非参数检验分析不同基因型的TYMP mRNA表达情况。结果:218例TYMP患者中rs11479的患病率显示，rs11479的次要等位基因频率为0.20 (GG 141例，GA 68例，AA 9例)，符合Hardy-Weinberg平衡(P=0.825)。相关性分析显示，GG基因型和GA/AA基因型患者的中位无病生存期(DFS)分别为3.1年和6.1年(P=0.004)。GG基因型和GA/AA基因型患者的中位总生存期分别为5.0年和7.0年(P=0.033)。多因素Cox回归分析显示，rs11479多态性是影响DFS的独立因素(HR = 1.64, P=0.009)。此外，在65例PBMC标本中，mRNA表达结果显示GA/AA基因型患者的TYMP mRNA表达量显著高于GG基因型患者(p结论:TYMP基因rs11479多态性可能通过介导TYMP mRNA表达来预测卡培他滨辅助化疗的结直肠癌患者的预后。本研究结论应在后续的前瞻性临床试验中得到验证。

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来源期刊

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.