TRPA1基因多态性影响中国人群顺铂所致肾毒性的风险。

IF 4.1 2区医学 Q1 ONCOLOGY

Translational Oncology Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI:10.1016/j.tranon.2025.102486

Cong Wang, Guifei Deng, Siyu Niu, Xianglong Meng

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引用次数: 0

摘要

导读：顺铂引起的不可逆急性肾损伤（AKI）限制了其临床应用，瞬时受体电位锚定蛋白1 （TRPA1）通过NF-κB信号通路介导的炎症调节顺铂诱导的肾毒性（CIN）。TRPA1和NF-κB1基因的单核苷酸多态性可能与个体异质肾毒性有关。材料与方法：研究了TRPA1和NF-κB1基因17个单核苷酸多态性（SNP）与顺铂急性肾毒性的关系。根据不良事件通用术语标准（CTCAE 5.0）评估肾毒性及其严重程度。采用48-Plex SNPscan®高通量SNP分型技术对589例接受顺铂治疗的中国汉族肺癌患者（CIN 241例，非CIN 348例）外周血DNA进行SNP检测。结果：TRAP1基因rs920829位点T等位基因携带者的肾毒性风险较C等位基因携带者低（OR 0.684, 95% CI 0.524 ~ 0.894, p = 0.003），其加性模型和显性模型表现出相似的趋势。然而，未观察到NF-κB1的snp与肾毒性相关。结论：TRPA1的snp有可能作为顺铂肾毒性预测的生物标志物。

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Genetic polymorphisms of TRPA1 does affect risk of cisplatin induced nephrotoxicity in Chinese population.

Introduction: Irreversible acute kidney injury (AKI) caused by cisplatin limits its clinical use, and transient receptor potential anchor protein 1 (TRPA1) regulates cisplatin-induced nephrotoxicity (CIN) through NF-κB signaling pathway-mediated inflammation. Single nucleotide polymorphisms in TRPA1 and NF-κB1 genes may be associated with individual heterogeneous nephrotoxicity.

Materials and methods: In this paper, we investigated the association of 17 single nucleotide polymorphisms (SNP) of TRPA1 and NF-κB1 genes with cisplatin-induced acute nephrotoxicity. Nephrotoxicity and its severity were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0). SNPs were measured by 48-Plex SNPscan® high-throughput SNP typing echnology in DNA isolated from peripheral blood of 589 Chinese Han lung cancer patients (241 with CIN and 348 without CIN) treated with cisplatin regimen.

Results: TRAP1 gene rs920829 locus T allele carriers had a reduced risk of nephrotoxicity relative to C allele carriers (OR 0.684, 95 % CI 0.524-0.894, p = 0.003), and their additive and dominant models showed similar trends as well. However, the SNPs of NF-κB1 were not observed to be correlated with nephrotoxicity.

Conclusion: SNPs of TRPA1 have the potential as biomarkers for predicting cisplatin nephrotoxicity.

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来源期刊

Translational Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

7.20

自引率

2.00%

发文量

314

审稿时长

6-12 weeks

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.