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The composition of an individual\u2019s 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\u2013 and PSA-matched White patients. These observations highlight the importance of controlling for race\u2013 and ancestry-associated differences in the development of urinary biomarkers.<\/jats:p>","DOI":"10.1101\/2025.08.14.670396","type":"posted-content","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T06:25:13Z","timestamp":1755671113000},"source":"Crossref","is-referenced-by-count":0,"title":["Ancestry-Dependent Immunologic and Prognostic Effects Characterize the Prostate Cancer Urinary Proteome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8740-4125","authenticated-orcid":false,"given":"Annie","family":"Ha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4218-2458","authenticated-orcid":false,"given":"Jaron","family":"Arbet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2510-7069","authenticated-orcid":false,"given":"Zhuyu","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8917-918X","authenticated-orcid":false,"given":"Amanda","family":"Khoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4527-4323","authenticated-orcid":false,"given":"Brian P","family":"Main","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meinusha","family":"Govindarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4537-1502","authenticated-orcid":false,"given":"Matthew","family":"Waas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6851-0857","authenticated-orcid":false,"given":"Stanley K","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9927-4869","authenticated-orcid":false,"given":"O John","family":"Semmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2854-7510","authenticated-orcid":false,"given":"Julius O","family":"Nyalwidhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-7520","authenticated-orcid":false,"given":"Paul C","family":"Boutros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-5540","authenticated-orcid":false,"given":"Thomas","family":"Kislinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025082201151524000_2025.08.14.670396v1.1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.R800001-MCP200"},{"key":"2025082201151524000_2025.08.14.670396v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-021-00500-1"},{"key":"2025082201151524000_2025.08.14.670396v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2009.261"},{"key":"2025082201151524000_2025.08.14.670396v1.4","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41585-019-0178-2","article-title":"Merging new-age biomarkers and nanodiagnostics for precision prostate cancer management","volume":"16","year":"2019","journal-title":"Nat Rev Urol"},{"key":"2025082201151524000_2025.08.14.670396v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.04.039"},{"key":"2025082201151524000_2025.08.14.670396v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49424-5"},{"key":"2025082201151524000_2025.08.14.670396v1.7","doi-asserted-by":"crossref","first-page":"e0304803","DOI":"10.1371\/journal.pone.0304803","article-title":"Differences in urine creatinine and osmolality between black and white Americans after accounting for age, moisture intake, urine volume, and socioeconomic status","volume":"19","year":"2024","journal-title":"PLoS One"},{"key":"2025082201151524000_2025.08.14.670396v1.8","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21874"},{"key":"2025082201151524000_2025.08.14.670396v1.9","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.r50"},{"key":"2025082201151524000_2025.08.14.670396v1.10","doi-asserted-by":"crossref","unstructured":"Garraway, I. 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