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[接受以卡培他滨为基础的辅助化疗的胃癌患者的临床结局及相应的药物基因组学分析]

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

作者信息

Chen W C, Wu G, Zhang W, Zhu Y Z, Zhou Y, Zhang H, Xia X B, Sun P C

机构信息

Department of Gastrointestinal Surgery, the People's Hospital of Zhengzhou University, Zhengzhou 450003, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2018 Nov 13;98(42):3420-3425. doi: 10.3760/cma.j.issn.0376-2491.2018.42.009.

Abstract

To investigate the association between Thymidine phosphorylase(TYMP)genetic variation and clinical outcomes of postoperative gastric cancer (GC) patients received capecitabine based regimens. A total of 198 GC patients underwent surgical treatment and received capecitabine based adjuvant chemotherapy were included in this retrospective study. Peripheral blood and the postoperative tissue specimen of the GC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative GC patients were analysed. Located in the upstream, rs11479 was of clinical significance. The prevalence of rs11479 in TYMP among the GC patients were as follows: CC genotype 125 cases (63.13%), CT genotype 65 cases (32.83%), TT genotype 8 cases (4.04%), minor allele frequency of rs11479 is 0.20. The distribution of three genotypes were in accordance with Hardy-Weinberg Equilibrium (=0.901). The analysis results of patients with different genotypes found that the 3-year disease free survival rate of the patients with CT/TT genotype and CC genotype were 73.97% and 65.60%, respectively, which was statistically significant (=0.003). In terms of overall survival, the 3-year overall survival rate of the two genotypes were 83.56% and 72.80% (=0.012), respectively. Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for disease free survival (=0.55, =0.011). Safety analysis indicated that there was no significant association between genotypes and grade 2 adverse reaction. Additionally, of the 79 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the wild type CC genotype patients (<0.001). The polymorphism rs11479 of TYMP have favorable influence on the clinical outcomes of gastric cancer patients received capecitabine based adjuvant chemotherapy treatment through changing the mRNA expression of TYMP.

摘要

为研究胸苷磷酸化酶(TYMP)基因变异与接受基于卡培他滨方案治疗的胃癌(GC)患者术后临床结局之间的关联。本回顾性研究纳入了198例行手术治疗并接受基于卡培他滨的辅助化疗的GC患者。分别采集GC患者的外周血和术后组织标本用于多态性基因分型和TYMP mRNA表达检测。分析多态性与术后GC患者临床结局及安全性之间的相关性。位于上游的rs11479具有临床意义。GC患者中TYMP基因rs11479的基因型分布如下:CC基因型125例(63.13%),CT基因型65例(32.83%),TT基因型8例(4.04%),rs11479的次要等位基因频率为0.20。三种基因型的分布符合Hardy-Weinberg平衡(=0.901)。不同基因型患者的分析结果显示,CT/TT基因型和CC基因型患者的3年无病生存率分别为73.97%和65.60%,差异有统计学意义(=0.003)。在总生存方面,两种基因型的3年总生存率分别为83.56%和72.80%(=0.012)。经多因素Cox回归分析校正后,CT/TT基因型是无病生存的独立有利因素(=0.55,=0.011)。安全性分析表明,基因型与2级不良反应之间无显著关联。此外,在79例术后组织标本中,结果显示CT/TT基因型患者癌组织中TYMP的表达明显高于野生型CC基因型患者(<0.001)。TYMP基因的多态性rs11479通过改变TYMP的mRNA表达,对接受基于卡培他滨辅助化疗的胃癌患者的临床结局有有利影响。

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