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CTR1、CTR2、ATP7A和ATP7B基因多态性与上皮性卵巢癌铂耐药性的相关性

Association between polymorphisms in CTR1, CTR2, ATP7A, and ATP7B and platinum resistance in epithelial ovarian cancer.

作者信息

Li Tailin, Peng Jingbo, Zeng Feiyue, Zhang Keqiang, Liu Jinyang, Li Xi, Ouyang Qianying, Wang Guo, Wang Liansheng, Liu Zhaoqian, Liu Yingzi

出版信息

Int J Clin Pharmacol Ther. 2017 Oct;55(10):774-780. doi: 10.5414/CP202907.

Abstract

The copper transporters CTR1, CTR2, ATP7A, and ATP7B regulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms in CTR1, CTR2, ATP7A, and ATP7B on platinum resistance in patients suffering from epithelial ovarian cancer (EOC). A total of 152 Chinese EOC patients were enrolled in this study, all of whom underwent adjuvant chemotherapy using platinum and taxane after maximal debulking surgery. In total, 11 single-nucleotide polymorphisms (SNPs) in CTR1, CTR2, ATP7A, and ATP7B were genotyped in these patients. The CTR1 rs10981694 polymorphism was observed to be associated with carboplatin resistance, while patients with the rs10981694 G allele showed a significantly higher rate of carboplatin resistance (OR = 4.00, 95% CI 1.309 - 12.23, p < 0.01). In addition, we found that ATP7A rs2227291 was associated with cisplatin resistance and that carriers of the C allele were more sensitive to cisplatin (OR = 0.40, 95% CI: 0.17 - 0.94, p = 0.03). Our findings suggest that the CTR1 and ATP7A genetic polymorphisms could affect platinum resistance. The CTR1 and ATP7A genes might be considered a predictive marker for carboplatin and cisplatin resistance, respectively.
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摘要

铜转运蛋白CTR1、CTR2、ATP7A和ATP7B通过介导铂在细胞内的摄取和外排来调节细胞内铂的浓度。我们试图探讨CTR1、CTR2、ATP7A和ATP7B基因多态性对上皮性卵巢癌(EOC)患者铂耐药性的影响。本研究共纳入152例中国EOC患者,所有患者在接受最大程度减瘤手术后均接受了铂类和紫杉烷辅助化疗。对这些患者的CTR1、CTR2、ATP7A和ATP7B中的11个单核苷酸多态性(SNP)进行了基因分型。观察到CTR1 rs10981694多态性与卡铂耐药相关,rs10981694 G等位基因的患者卡铂耐药率显著更高(OR = 4.00,95%CI 1.309 - 12.23,p < 0.01)。此外,我们发现ATP7A rs2227291与顺铂耐药相关,C等位基因携带者对顺铂更敏感(OR = 0.40,95%CI:0.17 - 0.94,p = 0.03)。我们的研究结果表明,CTR1和ATP7A基因多态性可能影响铂耐药性。CTR1和ATP7A基因可能分别被视为卡铂和顺铂耐药的预测标志物。

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