{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:18:49Z","timestamp":1791335929002,"version":"4.3.1"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["isevjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Extracellular Bio"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Bladder cancer (BCa) exhibits molecular heterogeneity that complicates early diagnosis and prognosis, and drives confounding clinical outcomes. Non\u2010muscle invasive and muscle\u2010invasive subtypes, especially for intermediate to high grade, carry a 25%\u201350% progression\u2010free survival rate, underscoring the need for high\u2010precision prognostic strategy. Urinary extracellular vesicles (uEVs) are promising carriers of tumour\u2010derived RNAs and proteins. However, significant challenges in studying uEVs arise from the diverse cellular origin of uEVs associated with the dynamic composition of urine, which presents roadblocks for developing the clinical utility of uEVs. We developed an AI\u2010driven EV liquid biopsy pipeline that integrates (1) standardised EV isolation via NanoPom magnetic beads, (2) transcriptomic profiling for molecular subtyping and (3) prognostic scoring algorithm. In a discovery cohort of 16 BCa patients including both muscle\u2010invasive bladder cancer (MIBC) and non\u2010muscle\u2010invasive bladder cancer (NMIBC), we compared NanoPom isolated uEVs with ExoEasy and Fujifilm MagCapture isolated uEVs, for identifying BCa subtype\u2010specific gene signatures, and externally validated them using UCSC Xena. The result outperformed currently reported BCa diagnostic biomarkers from assays including Galeas, CxBladder and Xpert. In a validation cohort composed of seven individuals with MIBC, NMIBC and healthy individuals, we confirmed with plasma\u2010derived EVs for correlating with uEV biomarkers from NGS sequencing. The prognostic score stratified patients into low\u2010, intermediate\u2010 and high\u2010grade risk groups based on Xena's BCa survival outcomes. Our AI\u2010driven uEV liquid biopsy pipeline proves the concept for high precision BCa subtyping and prognosis, which could potentially facilitate treatment decision and lead to advanced profiling of bladder tumour biology using uEV liquid biopsy.<\/jats:p>","DOI":"10.1002\/jex2.70141","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:05:42Z","timestamp":1777575942000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Urinary Extracellular Vesicles for High\u2010Precision Bladder Cancer Subtyping and Prognosis"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-2694","authenticated-orcid":false,"given":"Zachary F.","family":"Greenberg","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarun","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Kahn","sequence":"additional","affiliation":[{"name":"Department of Computer and Information Science and Engineering Herbert Wertheim College of Engineering University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiley S.","family":"Graim","sequence":"additional","affiliation":[{"name":"Department of Computer and Information Science and Engineering Herbert Wertheim College of Engineering University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padraic","family":"O'Malley","sequence":"additional","affiliation":[{"name":"Department of Urology College of Medicine University of Florida  Gainesville Florida USA"},{"name":"University of Florida Health Cancer Institute  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5316-9326","authenticated-orcid":false,"given":"Mei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy University of Florida  Gainesville Florida USA"},{"name":"University of Florida Health Cancer Institute  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-019-03035-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158544"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.4c00199"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1972.tb00899.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.102121"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12402"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12093"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2004.06.003"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-05430-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1109\/TSSC.1969.300225"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0546-8"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-024-00682-x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.256388.119"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03527-3"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03527-3"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vesic.2025.100093"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3259"},{"key":"e_1_2_10_22_1","first-page":"723","article-title":"A Kernel Two\u2010Sample Test","volume":"13","author":"Gretton A.","year":"2012","journal-title":"Journal of Machine Learning Research"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1607591"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03598-0"},{"key":"e_1_2_10_25_1","first-page":"29","article-title":"Early\u2010Stage Multi\u2010Cancer Detection Using an Extracellular Vesicle Protein\u2010Based Blood Test","volume":"2","author":"Hinestrosa J. 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