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依赖于祖先的免疫和预后效应是前列腺癌尿液蛋白质组的特征。

Ancestry-Dependent Immunologic and Prognostic Effects Characterize the Prostate Cancer Urinary Proteome.

作者信息

Ha Annie, Arbet Jaron, Qiu Zhuyu, Khoo Amanda, Main Brian P, Govindarajan Meinusha, Waas Matthew, Liu Stanley K, Semmes O John, Nyalwidhe Julius O, Boutros Paul C, Kislinger Thomas

机构信息

Department of Medical Biophysics, University of Toronto, Toronto, Canada.

Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.

出版信息

bioRxiv. 2025 Aug 19:2025.08.14.670396. doi: 10.1101/2025.08.14.670396.

DOI:10.1101/2025.08.14.670396
PMID:40894632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12393444/
Abstract

Urine is an attractive biomarker analyte for non-invasive longitudinal monitoring of health and disease, particularly for diseases of the genitourinary tract, like prostate and bladder cancer. The composition of an individual's urine reflects both genetic and lifestyle characteristics that differ across geographies and populations, like diet, hydration and other socio-economic factors. While men of African ancestry have elevated prostate cancer risk, it is unclear to what extent this influences urinary biomarkers. We therefore quantified the urinary proteomes of 329 localized prostate cancer patients: 135 self-identifying as White and 194 self-identifying as Black. We identified 110 proteins that significantly differed between these groups after controlling for age, PSA, and cISUP. Immune pathways were particularly dysregulated. The urinary proteome of Black patients harboured more features of aggressive cancers than those of grade- and PSA-matched White patients. These observations highlight the importance of controlling for race- and ancestry-associated differences in the development of urinary biomarkers.

摘要

尿液是用于健康和疾病无创纵向监测的一种有吸引力的生物标志物分析物,特别是对于泌尿生殖道疾病,如前列腺癌和膀胱癌。个体尿液的成分反映了不同地理区域和人群之间的遗传和生活方式特征,如饮食、水合作用和其他社会经济因素。虽然非洲裔男性患前列腺癌的风险较高,但尚不清楚这在多大程度上影响尿液生物标志物。因此,我们对329例局限性前列腺癌患者的尿液蛋白质组进行了定量分析:135例自我认定为白人,194例自我认定为黑人。在控制年龄、前列腺特异性抗原(PSA)和国际泌尿病理学会(ISUP)分级后,我们鉴定出110种在这些组之间有显著差异的蛋白质。免疫途径尤其失调。与年龄和PSA匹配的白人患者相比,黑人患者的尿液蛋白质组具有更多侵袭性癌症的特征。这些观察结果突出了在尿液生物标志物开发中控制种族和血统相关差异的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd28/12393444/f6447242aeda/nihpp-2025.08.14.670396v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd28/12393444/17518c7f4c66/nihpp-2025.08.14.670396v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd28/12393444/bbdc69692d5a/nihpp-2025.08.14.670396v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd28/12393444/c4446672d035/nihpp-2025.08.14.670396v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd28/12393444/f6447242aeda/nihpp-2025.08.14.670396v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd28/12393444/17518c7f4c66/nihpp-2025.08.14.670396v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd28/12393444/bbdc69692d5a/nihpp-2025.08.14.670396v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd28/12393444/c4446672d035/nihpp-2025.08.14.670396v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd28/12393444/f6447242aeda/nihpp-2025.08.14.670396v1-f0004.jpg

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本文引用的文献

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Cancer statistics for African American and Black people, 2025.2025年非裔美国人和黑人的癌症统计数据。
CA Cancer J Clin. 2025 Mar-Apr;75(2):111-140. doi: 10.3322/caac.21874. Epub 2025 Feb 20.
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The Germline and Somatic Origins of Prostate Cancer Heterogeneity.前列腺癌异质性的种系和体细胞起源
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Black men have higher rates of late stage prostate cancer, audit shows.审计显示,黑人男性晚期前列腺癌的发病率更高。
BMJ. 2025 Jan 10;388:r50. doi: 10.1136/bmj.r50.
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Prostate cancer reshapes the secreted and extracellular vesicle urinary proteomes.前列腺癌重塑分泌型和细胞外囊泡尿液蛋白质组。
Nat Commun. 2024 Jun 13;15(1):5069. doi: 10.1038/s41467-024-49424-5.
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Differences in urine creatinine and osmolality between black and white Americans after accounting for age, moisture intake, urine volume, and socioeconomic status.考虑到年龄、水分摄入、尿量和社会经济地位后,美国黑人和白人的尿肌酐和渗透压差异。
PLoS One. 2024 May 31;19(5):e0304803. doi: 10.1371/journal.pone.0304803. eCollection 2024.
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Prostate Cancer Foundation Screening Guidelines for Black Men in the United States.美国黑人男性前列腺癌基金会筛查指南
NEJM Evid. 2024 May;3(5):EVIDoa2300289. doi: 10.1056/EVIDoa2300289. Epub 2024 Apr 23.
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Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer.开发和验证一种用于高级别前列腺癌的 18 基因尿液检测方法。
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Comprehensive Prostate Fluid-Based Spectral Libraries for Enhanced Protein Detection in Urine.用于增强尿液中蛋白质检测的基于前列腺液的综合光谱库
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Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part I: Introduction and Treatment Decision-Making at the Time of Suspected Biochemical Recurrence after Radical Prostatectomy.前列腺癌挽救性治疗:AUA/ASTRO/SUO 指南第 I 部分:根治性前列腺切除术后疑似生化复发时的介绍和治疗决策。
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