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作为肾细胞癌的潜在生物标志物:来自综合遗传分析的证据。

as a Potential Biomarker for Renal Cell Carcinoma: Evidence from an Integrated Genetic Analysis.

机构信息

Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan, R.O.C.

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C.

出版信息

Cancer Genomics Proteomics. 2023 Sep-Oct;20(5):469-475. doi: 10.21873/cgp.20398.

Abstract

BACKGROUND/AIM: Oxidative stress plays an important role in various pathogenic processes, and disruption in the coordinated production of NADPH oxidase (NOX)-derived reactive oxygen species has been associated with carcinogenesis. However, little is known about whether genetic variants in NOX can contribute to the development of renal cell carcinoma (RCC).

PATIENTS AND METHODS

This study aimed to bridge this knowledge gap by analysing the association of 10 single-nucleotide polymorphisms in the phagocyte NOX genes, CYBA and CYBB, with RCC risk and tumour characteristics in 630 RCC patients and controls. Differential gene expression and patient prognosis analyses were performed using gene expression data obtained from public databases.

RESULTS

Multivariate analysis and multiple testing corrections revealed the A allele of rs7195830 in CYBA to be a significant risk allele for RCC, compared to the G allele [odds ratio (OR)=1.70, 95% confidence interval (CI)=1.27-2.26, p<0.001]. A pooled analysis of 17 renal cancer gene expression datasets revealed a higher CYBA expression in RCC than in normal tissues. Moreover, high CYBA expression was associated with advanced tumour characteristics and worse patient prognosis.

CONCLUSION

CYBA might play an oncogenic role in RCC and serve as a predictive indicator of patient prognosis.

摘要

背景/目的:氧化应激在各种致病过程中起着重要作用,而 NADPH 氧化酶(NOX)衍生的活性氧产生的协调破坏与癌症发生有关。然而,关于 NOX 中的遗传变异是否会导致肾细胞癌(RCC)的发展知之甚少。

患者和方法

本研究旨在通过分析吞噬细胞 NOX 基因 CYBA 和 CYBB 中的 10 个单核苷酸多态性与 630 例 RCC 患者和对照者的 RCC 风险和肿瘤特征之间的关系来填补这一知识空白。使用从公共数据库获得的基因表达数据进行差异基因表达和患者预后分析。

结果

多变量分析和多重测试校正显示,与 G 等位基因相比,CYBA 中的 rs7195830 的 A 等位基因是 RCC 的显著风险等位基因[比值比(OR)=1.70,95%置信区间(CI)=1.27-2.26,p<0.001]。对 17 个肾肿瘤基因表达数据集的汇总分析显示,RCC 中的 CYBA 表达高于正常组织。此外,高 CYBA 表达与晚期肿瘤特征和患者预后不良相关。

结论

CYBA 可能在 RCC 中发挥致癌作用,并可作为患者预后的预测指标。

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Genetic Analysis Identifies the Role of in Renal Cell Carcinoma.遗传分析确定在肾细胞癌中的作用。
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本文引用的文献

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NOX Dependent ROS Generation and Cell Metabolism.NOX 依赖性 ROS 生成与细胞代谢。
Int J Mol Sci. 2023 Jan 20;24(3):2086. doi: 10.3390/ijms24032086.
7
Genetic Analysis Identifies the Role of in Renal Cell Carcinoma.遗传分析确定在肾细胞癌中的作用。
Cancer Genomics Proteomics. 2020 Nov-Dec;17(6):827-833. doi: 10.21873/cgp.20236.
8
Molecular insights of NADPH oxidases and its pathological consequences.NADPH 氧化酶及其病理后果的分子见解。
Cell Biochem Funct. 2021 Mar;39(2):218-234. doi: 10.1002/cbf.3589. Epub 2020 Sep 25.

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