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线粒体DNA拷贝数评估是白人而非黑人前列腺癌的有力预测指标。

Mitochondrial DNA copy number assessment is a potent predictor for prostate cancer in White but not Black Individuals.

作者信息

Flores Melanie K, Janes Jessica L, Islam Mirajul, Wan Junxiang, Liu Jiali, Reams Romonia R, Su Li-Ming, Yen Kelvin, Mehta Hemal H, Reagan Allison, Howard Lauren E, Wiggins Emily, Vidal Adriana C, Freedland Stephen J, Cohen Pinchas

机构信息

University of Southern California, Los Angeles, United States.

Durham VA Health Care System, Durham, North Carolina, United States.

出版信息

Cancer Prev Res (Phila). 2025 May 13. doi: 10.1158/1940-6207.CAPR-24-0401.

Abstract

Black individuals are disproportionately burdened by prostate cancer compared to White individuals. The mitochondrion is an untapped source for prostate cancer (PCa) biomarkers, and previous work has shown altered mitochondrial DNA (mtDNA) copy number is linked to mitochondrial dysfunction and tumorigenesis. We assess whether mtDNA copy number is altered in patients with and without PCa in a racially specific manner. Circulating cell-free mtDNA copy number from plasma and mtDNA copy number from white blood cells (WBCs) were measured in 199 patients undergoing biopsy (50/50 White cases/controls and 50/49 Black cases/controls). MtDNA copy number was determined via ddPCR. Logistic regressions tested associations between mtDNA and PCa by race. The area under the curve (AUC) was compared between covariate-only models and models with mtDNA. In both plasma and WBCs, mtDNA copy number was significantly increased in cases compared to controls in White patients, but not in Black patients. Interestingly, Black controls had higher mtDNA copy number levels than White controls. Multivariable analysis revealed significant associations of Plasma mtDNA and WBC mtDNA with PCa for White patients only. Elevated mtDNA copy number was more accurate in predicting PCa in White patients than in Black patients. Higher mtDNA copy number levels were associated with PCa in both Black and White patients. Plasma mtDNA may be more accurate than WBC mtDNA in predicting PCa incidence in Black men. Overall, Black controls had higher mtDNA copy number levels than White controls, suggesting mtDNA copy number may be implicated in PCa health disparities.

摘要

与白人相比,黑人患前列腺癌的负担过重。线粒体是前列腺癌(PCa)生物标志物的一个未开发来源,先前的研究表明线粒体DNA(mtDNA)拷贝数的改变与线粒体功能障碍和肿瘤发生有关。我们评估mtDNA拷贝数在患有和未患有PCa的患者中是否存在种族特异性变化。在199例接受活检的患者(50/50白人病例/对照和50/49黑人病例/对照)中测量了血浆中循环游离mtDNA拷贝数和白细胞(WBC)中的mtDNA拷贝数。通过数字 droplet 聚合酶链反应(ddPCR)确定mtDNA拷贝数。逻辑回归按种族测试了mtDNA与PCa之间的关联。比较了仅含协变量模型和含mtDNA模型的曲线下面积(AUC)。在血浆和WBC中,与对照组相比,白人患者病例中的mtDNA拷贝数显著增加,但黑人患者中未增加。有趣的是,黑人对照组的mtDNA拷贝数水平高于白人对照组。多变量分析显示,仅白人患者的血浆mtDNA和WBC mtDNA与PCa有显著关联。mtDNA拷贝数升高在预测白人患者的PCa方面比黑人患者更准确。在黑人和白人患者中,较高的mtDNA拷贝数水平均与PCa相关。血浆mtDNA在预测黑人男性PCa发病率方面可能比WBC mtDNA更准确。总体而言,黑人对照组的mtDNA拷贝数水平高于白人对照组,这表明mtDNA拷贝数可能与PCa健康差异有关。

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