{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:31:36Z","timestamp":1777480296629,"version":"3.51.4"},"reference-count":109,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011776","name":"Instituto Portugu\u00eas de Oncologia do Porto","doi-asserted-by":"publisher","award":["CI-IPOP-PI27-FB-GEBC"],"award-info":[{"award-number":["CI-IPOP-PI27-FB-GEBC"]}],"id":[{"id":"10.13039\/501100011776","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-030831"],"award-info":[{"award-number":["POCI-01-0145-FEDER-030831"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BTM-TEC\/30831\/2017"],"award-info":[{"award-number":["PTDC\/BTM-TEC\/30831\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019179","name":"Fundaci\u00f3n Bancaria Caixa d'Estalvis i Pensions de Barcelona","doi-asserted-by":"publisher","award":["LCF\/BQ\/DR20\/11790013"],"award-info":[{"award-number":["LCF\/BQ\/DR20\/11790013"]}],"id":[{"id":"10.13039\/501100019179","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Urologic cancers are a heterogeneous group of tumors, some of which have poor prognosis. This is partly due to the unavailability of specific and sensitive diagnostic techniques and monitoring tests, ideally non- or minimally invasive. Hence, liquid biopsies are promising tools that have been gaining significant attention over the last decade. Among the different classes of biomarkers that can be isolated from biofluids, urinary extracellular vesicles (uEVs) are a promising low-invasive source of biomarkers, with the potential to improve cancer diagnosis and disease management. Different techniques have been developed to isolate and characterize the cargo of these vesicles; however, no consensus has been reached, challenging the comparison among studies. This results in a vast number of studies portraying an extensive list of uEV-derived candidate biomarkers for urologic cancers, with the potential to improve clinical outcome; however, without significant validation. Herein, we review the current published research on miRNA and protein-derived uEV for prostate, bladder and kidney cancers, focusing on different uEV isolation methods, and its implications for biomarker studies.<\/jats:p>","DOI":"10.3390\/cancers13071529","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T13:17:53Z","timestamp":1616764673000},"page":"1529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Urinary Extracellular Vesicles as Potential Biomarkers for Urologic Cancers: An Overview of Current Methods and Advances"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0644-0202","authenticated-orcid":false,"given":"Catarina","family":"Louren\u00e7o","sequence":"first","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"INEB-Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"IPO Porto Research Center (CBEG CI-IPOP), Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3151-0367","authenticated-orcid":false,"given":"Vera","family":"Const\u00e2ncio","sequence":"additional","affiliation":[{"name":"IPO Porto Research Center (CBEG CI-IPOP), Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"IPO Porto Research Center (CBEG CI-IPOP), Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4837-6539","authenticated-orcid":false,"given":"\u00c2ngela","family":"Carvalho","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"INEB-Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"IPO Porto Research Center (CBEG CI-IPOP), Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"Cancer J. Clin."},{"key":"ref_2","unstructured":"Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2020, December 21). Available online: https:\/\/gco.iarc.fr\/today."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.mric.2014.01.002","article-title":"MR imaging-guided prostate biopsy techniques","volume":"22","author":"Verma","year":"2014","journal-title":"Magn. Reson. Imaging Clin. N. Am."},{"key":"ref_4","first-page":"507","article-title":"Bladder Cancer: Diagnosis and Treatment","volume":"96","author":"DeGeorge","year":"2017","journal-title":"Am. Fam. Phys."},{"key":"ref_5","first-page":"508","article-title":"Renal cancer","volume":"37","author":"Blecher","year":"2019","journal-title":"Surg. Oxf. Int. Ed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.eururo.2016.10.008","article-title":"Global Burden of Urologic Cancers, 1990\u20132013","volume":"71","author":"Dy","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1080\/14737159.2019.1604224","article-title":"Known epigenetic biomarkers for prostate cancer detection and management: Exploring the potential of blood-based liquid biopsies","volume":"19","author":"Henrique","year":"2019","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nrurol.2016.224","article-title":"Circulating tumour cells as biomarkers of prostate, bladder, and kidney cancer","volume":"14","author":"Gorin","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.juro.2012.04.143","article-title":"Toward the detection of prostate cancer in urine: A critical analysis","volume":"189","author":"Truong","year":"2013","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1443.e9","DOI":"10.1016\/j.urology.2014.02.013","article-title":"Detection of bladder cancer by measuring CD44v6 expression in urine with real-time quantitative reverse transcription polymerase chain reaction","volume":"83","author":"Hattori","year":"2014","journal-title":"Urology"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kistler, A.D., Serra, A.L., Siwy, J., Poster, D., Krauer, F., Torres, V.E., Mrug, M., Grantham, J.J., Bae, K.T., and Bost, J.E. (2013). Urinary Proteomic Biomarkers for Diagnosis and Risk Stratification of Autosomal Dominant Polycystic Kidney Disease: A Multicentric Study. PLoS ONE, 8.","DOI":"10.1371\/annotation\/9281c713-d253-4a1a-8255-92e691e77a24"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Konoshenko, M.Y., Lekchnov, E.A., Vlassov, A.V., and Laktionov, P.P. (2018). Isolation of Extracellular Vesicles: General Methodologies and Latest Trends. Biomed Res. Int., 2018.","DOI":"10.1155\/2018\/8545347"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13368","DOI":"10.1073\/pnas.0403453101","article-title":"Identification and proteomic profiling of exosomes in human urine","volume":"101","author":"Pisitkun","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1093\/ndt\/gfn058","article-title":"Urinary exosomes: Is there a future?","volume":"23","author":"Gonzales","year":"2008","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Doyle, L.M., and Wang, M.Z. (2019). Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8.","DOI":"10.3390\/cells8070727"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1158\/0008-5472.CAN-17-0994","article-title":"The biology of cancer exosomes: Insights and new perspectives","volume":"77","author":"Ruivo","year":"2017","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.eururo.2016.02.046","article-title":"Extracellular Vesicles and Their Role in Urologic Malignancies","volume":"70","author":"Junker","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_19","first-page":"1","article-title":"An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer","volume":"7","author":"Liang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/pmic.201300389","article-title":"The roles of extracellular vesicles in cancer biology: Toward the development of novel cancer biomarkers","volume":"14","author":"Katsuda","year":"2014","journal-title":"Proteomics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Antimisiaris, S.G., Mourtas, S., and Marazioti, A. (2018). Exosomes and Exosome-Inspired Vesicles for Targeted Drug Delivery. Pharmaceutics, 10.","DOI":"10.20944\/preprints201810.0507.v1"},{"key":"ref_23","first-page":"1","article-title":"Exosome-mimetic nanoplatforms for targeted cancer drug delivery","volume":"17","author":"Bouzo","year":"2019","journal-title":"J. Nanobiotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gerlach, J.Q., Kr\u00fcger, A., Gallogly, S., Hanley, S.A., Hogan, M.C., Ward, C.J., Joshi, L., and Griffin, M.D. (2013). Surface Glycosylation Profiles of Urine Extracellular Vesicles. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074801"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nmeth.4185","article-title":"EV-TRACK: Transparent reporting and centralizing knowledge in extracellular vesicle research","volume":"14","author":"Mestdagh","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/ki.2009.550","article-title":"Tamm-Horsfall protein and urinary exosome isolation","volume":"77","author":"Khositseth","year":"2010","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/ki.2010.262","article-title":"Comparison of three methods for isolation of urinary microvesicles to identify biomarkers of nephrotic syndrome","volume":"78","author":"Rood","year":"2010","journal-title":"Kidney Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1038\/ki.2012.256","article-title":"Comparison of protein, microRNA, and mRNA yields using different methods of urinary exosome isolation for the discovery of kidney disease biomarkers","volume":"82","author":"Alvarez","year":"2012","journal-title":"Kidney Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1515\/cclm-2013-0562","article-title":"Optimizing the purification and analysis of miRNAs from urinary exosomes","volume":"52","author":"Channavajjhala","year":"2014","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"29497","DOI":"10.3402\/jev.v5.29497","article-title":"Different EV enrichment methods suitable for clinical settings yield different subpopulations of urinary extracellular vesicles from human samples","volume":"5","author":"Royo","year":"2016","journal-title":"J. Extracell. Vesicles"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.5772\/62579","article-title":"Protein Complexes in Urine Interfere with Extracellular Vesicle Biomarker Studies","volume":"5","author":"Wachalska","year":"2016","journal-title":"J. Circ. Biomark."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-22142-x","article-title":"Improved isolation strategies to increase the yield and purity of human urinary exosomes for biomarker discovery","volume":"8","author":"Gheinani","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_33","first-page":"83","article-title":"A highly efficient method for isolating urinary exosomes","volume":"43","author":"He","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.procbio.2019.09.017","article-title":"Development and comparative analysis of human urine exosome isolation strategies","volume":"88","author":"Cho","year":"2020","journal-title":"Process Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1736935","DOI":"10.1080\/20013078.2020.1736935","article-title":"Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine","volume":"9","author":"Dhondt","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhou, M., Weber, S.R., Zhao, Y., Chen, H., and Sundstrom, J.M. (2020). Methods for exosome isolation and characterization. Exosomes, Elsevier Inc.","DOI":"10.1016\/B978-0-12-816053-4.00002-X"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.3892\/ol.2014.2373","article-title":"Comparison of ultracentrifugation and density gradient separation methods for isolating Tca8113 human tongue cancer cell line-derived exosomes","volume":"8","author":"Zhang","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ymeth.2012.01.002","article-title":"Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes","volume":"56","author":"Tauro","year":"2012","journal-title":"Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"F1657","DOI":"10.1152\/ajprenal.00434.2006","article-title":"Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator","volume":"292","author":"Cheruvanky","year":"2007","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/prca.200800093","article-title":"Microfiltration isolation of human urinary exosomes for characterization by MS","volume":"4","author":"Merchant","year":"2010","journal-title":"Proteom. Clin. Appl."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"27369","DOI":"10.3402\/jev.v4.27369","article-title":"Size-exclusion chromatography-based enrichment of extracellular vesicles from urine samples","volume":"4","author":"Bancu","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nrurol.2014.301","article-title":"The emerging role of extracellular vesicles as biomarkers for urogenital cancers","volume":"11","author":"Nawaz","year":"2014","journal-title":"Nat. Rev. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.bios.2016.12.062","article-title":"Microfluidic approaches for isolation, detection, and characterization of extracellular vesicles: Current status and future directions","volume":"91","author":"Gholizadeh","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5351","DOI":"10.1007\/s00216-019-01982-0","article-title":"Advances in exosome isolation methods and their applications in proteomic analysis of biological samples","volume":"411","author":"Hou","year":"2019","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1039\/C4LC00136B","article-title":"Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes","volume":"14","author":"Kanwar","year":"2014","journal-title":"Lab Chip"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10712","DOI":"10.1021\/acsnano.7b04878","article-title":"The Exosome Total Isolation Chip","volume":"11","author":"Liu","year":"2017","journal-title":"ACS Nano"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1039\/C8LC00834E","article-title":"Microfluidic affinity separation chip for selective capture and release of label-free ovarian cancer exosomes","volume":"18","author":"Hisey","year":"2018","journal-title":"Lab Chip"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1039\/C4LC00662C","article-title":"Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology","volume":"14","author":"He","year":"2014","journal-title":"Lab Chip"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1158\/0008-5472.CAN-18-3538","article-title":"A microfluidic chip enables isolation of exosomes and establishment of their protein profiles and associated signaling pathways in ovarian cancer","volume":"79","author":"Dorayappan","year":"2019","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41551-019-0356-9","article-title":"Ultrasensitive detection of circulating exosomes with a 3D-nanopatterned microfluidic chip","volume":"3","author":"Zhang","year":"2019","journal-title":"Nat. Biomed. Eng."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1021\/acsnano.6b06131","article-title":"Exodisc for Rapid, Size-Selective, and Efficient Isolation and Analysis of Nanoscale Extracellular Vesicles from Biological Samples","volume":"11","author":"Woo","year":"2017","journal-title":"ACS Nano"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1016\/j.bbagen.2016.07.028","article-title":"Methods for the physical characterization and quantification of extracellular vesicles in biological samples","volume":"1861","author":"Rupert","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/978-1-4939-7253-1_18","article-title":"Detection and Characterization of Extracellular Vesicles by Transmission and Cryo-Transmission Electron Microscopy","volume":"1660","author":"Cizmar","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"21494","DOI":"10.3402\/jev.v2i0.21494","article-title":"Cryo-electron microscopy of extracellular vesicles in fresh plasma","volume":"2","author":"Yuana","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.nano.2011.04.003","article-title":"Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis","volume":"7","author":"Dragovic","year":"2011","journal-title":"Nanomedicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/nep.12867","article-title":"Albuminuria is not associated with elevated urinary vesicle concentration but can confound nanoparticle tracking analysis","volume":"22","author":"McNicholas","year":"2017","journal-title":"Nephrology"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hartjes, T.A., Mytnyk, S., Jenster, G.W., van Steijn, V., and van Royen, M.E. (2019). Extracellular vesicle quantification and characterization: Common methods and emerging approaches. Bioengineering, 6.","DOI":"10.3390\/bioengineering6010007"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e12659","DOI":"10.1111\/cpr.12659","article-title":"Extracellular vesicles in urologic malignancies\u2014Implementations for future cancer care","volume":"52","author":"Wu","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_60","first-page":"179","article-title":"Altered proteome of extracellular vesicles derived from bladder cancer patients urine","volume":"41","author":"Lee","year":"2018","journal-title":"Mol. Cells"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"19","DOI":"10.6004\/jnccn.2016.0004","article-title":"Prostate Cancer, Version 1.2016","volume":"14","author":"Mohler","year":"2016","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"v69","DOI":"10.1093\/annonc\/mdv222","article-title":"Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up\u2020","volume":"26","author":"Parker","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Carlsson, S.V., and Vickers, A.J. (2020). Screening for Prostate Cancer. Med. Clin. N. Am.","DOI":"10.1016\/j.mcna.2020.08.007"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.eururo.2005.04.015","article-title":"Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2-10 ng\/mL: Systematic review and meta-analysis","volume":"48","author":"Roddam","year":"2005","journal-title":"Eur. Urol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/pros.23934","article-title":"Prostate cancer research: The next generation; report from the 2019 Coffey-Holden Prostate Cancer Academy Meeting","volume":"80","author":"Miyahira","year":"2020","journal-title":"Prostate"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"30357","DOI":"10.18632\/oncotarget.4851","article-title":"Identification of prostate cancer biomarkers in urinary exosomes","volume":"6","author":"Overbye","year":"2015","journal-title":"Oncotarget"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"31209","DOI":"10.3402\/jev.v5.31209","article-title":"Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array","volume":"5","author":"Welton","year":"2016","journal-title":"J. Extracell. Vesicles"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep42961","article-title":"Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer","volume":"7","author":"Fujita","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4960","DOI":"10.18632\/oncotarget.13634","article-title":"Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer","volume":"8","author":"Sequeiros","year":"2017","journal-title":"Oncotarget"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ejps.2016.09.023","article-title":"Exosomal proteins as prostate cancer biomarkers in urine: From mass spectrometry discovery to immunoassay-based validation","volume":"98","author":"Wang","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"22566","DOI":"10.18632\/oncotarget.8124","article-title":"Non\u2014Invasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles","volume":"7","author":"Hackenberg","year":"2016","journal-title":"Oncotarget"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Bryzgunova, O.E., Zaripov, M.M., Skvortsova, T.E., Lekchnov, E.A., Grigor\u2019eva, A.E., Zaporozhchenko, I.A., Morozkin, E.S., Ryabchikova, E.I., Yurchenko, Y.B., and Voitsitskiy, V.E. (2016). Comparative study of extracellular vesicles from the urine of healthy individuals and prostate cancer patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157566"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1002\/pros.23376","article-title":"MiR-145 detection in urinary extracellular vesicles increase diagnostic efficiency of prostate cancer based on hydrostatic filtration dialysis method","volume":"77","author":"Xu","year":"2017","journal-title":"Prostate"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jbiotec.2017.07.029","article-title":"Urinary-exosomal miR-2909: A novel pathognomonic trait of prostate cancer severity","volume":"259","author":"Wani","year":"2017","journal-title":"J. Biotechnol."},{"key":"ref_75","first-page":"4","article-title":"Identification of non-invasive miRNAs biomarkers for prostate cancer by deep sequencing analysis of urinary exosomes","volume":"16","author":"Hessvik","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/pros.23295","article-title":"Exosomal and Non-Exosomal Urinary miRNAs in Prostate Cancer Detection and Prognosis","volume":"77","author":"Foj","year":"2017","journal-title":"Prostate"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Bryzgunova, O.E., Zaporozhchenko, I.A., Lekchnov, E.A., Amelina, E.V., Konoshenko, M.Y., Yarmoschuk, S.V., Pashkovskaya, O.A., Zheravin, A.A., Pak, S.V., and Rykova, E.Y. (2019). Data analysis algorithm for the development of extracellular miRNA-based diagnostic systems for prostate cancer. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215003"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Davey, M., Benzina, S., Savoie, M., Breault, G., Ghosh, A., and Ouellette, R.J. (2020). Affinity Captured Urinary Extracellular Vesicles Provide mRNA and miRNA Biomarkers for Improved Accuracy of Prostate Cancer Detection: A Pilot Study. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218330"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4103\/0970-1591.166445","article-title":"Non-muscle invasive bladder cancer risk stratification","volume":"31","author":"Isharwal","year":"2015","journal-title":"Indian J. Urol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.eururo.2011.07.066","article-title":"External Validation of Postoperative Nomograms for Prediction of All-Cause Mortality, Cancer-Specific Mortality, and Recurrence in Patients With Urothelial Carcinoma of the Bladder","volume":"61","author":"Nuhn","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"100195","DOI":"10.1016\/j.ctarc.2020.100195","article-title":"Prognosis of patients with muscle invasive bladder cancer who are intolerable to receive any anti-cancer treatment","volume":"24","author":"Ogawa","year":"2020","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/MOU.0000000000000078","article-title":"The burden of bladder cancer care: Direct and indirect costs","volume":"24","author":"Mossanen","year":"2014","journal-title":"Curr. Opin. Urol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.eururo.2016.05.041","article-title":"EAU Guidelines on Non\u2013Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016","volume":"71","author":"Babjuk","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"De Oliveira, M.C., Caires, H.R., Oliveira, M.J., Fraga, A., Vasconcelos, M.H., and Ribeiro, R. (2020). Urinary biomarkers in bladder cancer: Where do we stand and potential role of extracellular vesicles. Cancers, 12.","DOI":"10.3390\/cancers12061400"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1021\/pr700775x","article-title":"Isolation and identification of potential urinary microparticle biomarkers of bladder cancer","volume":"7","author":"Smalley","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5611","DOI":"10.1021\/pr3008732","article-title":"Comparative and targeted proteomic analyses of urinary microparticles from bladder cancer and hernia patients","volume":"11","author":"Chen","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejps.2016.10.008","article-title":"Extracellular vesicles as a source for non-invasive biomarkers in bladder cancer progression","volume":"98","author":"Andreu","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_88","first-page":"1","article-title":"Proteome profiling of urinary exosomes identifies alpha 1-antitrypsin and H2B1K as diagnostic and prognostic biomarkers for urothelial carcinoma","volume":"6","author":"Lin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"91199","DOI":"10.18632\/oncotarget.20043","article-title":"Characterization of urinary extracellular vesicle proteins in muscle-invasive bladder cancer","volume":"8","author":"Silvers","year":"2017","journal-title":"Oncotarget"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-62753-x","article-title":"Urinary Exosomes from Bladder Cancer Patients Show a Residual Cancer Phenotype despite Complete Pathological Downstaging","volume":"10","author":"Hiltbrunner","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-015-0466-2","article-title":"MicroRNA molecular profiling from matched tumor and bio-fluids in bladder cancer","volume":"14","author":"Armstrong","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_92","first-page":"2500","article-title":"A non-invasive miRNA based assay to detect bladder cancer in cell-free urine","volume":"7","author":"Sullivan","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"24668","DOI":"10.18632\/oncotarget.14969","article-title":"MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma","volume":"8","author":"Matsuzaki","year":"2017","journal-title":"Oncotarget"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1007\/s00432-019-03035-6","article-title":"MicroRNAs in tumor samples and urinary extracellular vesicles as a putative diagnostic tool for muscle-invasive bladder cancer","volume":"145","author":"Baumgart","year":"2019","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"724","DOI":"10.3389\/fonc.2020.00724","article-title":"Extracellular Vesicles in Renal Cell Carcinoma: Multifaceted Roles and Potential Applications Identified by Experimental and Computational Methods","volume":"10","author":"Qin","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"79","DOI":"10.14740\/wjon1279","article-title":"Epidemiology of Renal Cell Carcinoma","volume":"11","author":"Padala","year":"2020","journal-title":"World J. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.eururo.2015.07.072","article-title":"Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy","volume":"69","author":"Marconi","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.3389\/fonc.2020.582843","article-title":"Liquid Biopsies in Renal Cell Carcinoma\u2014Recent Advances and Promising New Technologies for the Early Detection of Metastatic Disease","volume":"10","author":"Lakshminarayanan","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41585-019-0261-8","article-title":"Extracellular vesicles in urological malignancies: An update","volume":"17","author":"Linxweiler","year":"2020","journal-title":"Nat. Rev. Urol."},{"key":"ref_100","first-page":"1","article-title":"Renal cell carcinoma","volume":"3","author":"Hsieh","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S0094-0143(03)00056-9","article-title":"Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease","volume":"30","author":"Janzen","year":"2003","journal-title":"Urol. Clin. N. Am."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.clinbiochem.2012.11.029","article-title":"Proteomics and the search for biomarkers for renal cancer","volume":"46","author":"Craven","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"F1251","DOI":"10.1152\/ajprenal.00128.2014","article-title":"Urinary extracellular vesicles and the kidney: Biomarkers and beyond","volume":"306","author":"Salih","year":"2014","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1039\/c3mb25582d","article-title":"Differential protein profiling of renal cell carcinoma urinary exosomes","volume":"9","author":"Raimondo","year":"2013","journal-title":"Mol. Biosyst."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.euf.2015.11.006","article-title":"Exosomal MicroRNAs Are Diagnostic Biomarkers and Can Mediate Cell-Cell Communication in Renal Cell Carcinoma","volume":"2","author":"Butz","year":"2016","journal-title":"Eur. Urol. Focus"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6755","DOI":"10.1111\/jcmm.14553","article-title":"Urinary exosome miR-30c-5p as a biomarker of clear cell renal cell carcinoma that inhibits progression by targeting HSPA5","volume":"23","author":"Song","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1038\/sj.ki.5000273","article-title":"Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery","volume":"69","author":"Zhou","year":"2006","journal-title":"Kidney Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1021\/acs.jproteome.7b00763","article-title":"Effects of Hematuria on the Proteomic Profile of Urinary Extracellular Vesicles: Technical Challenges","volume":"17","author":"Raimondo","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/ki.2013.502","article-title":"Characterization and deep sequencing analysis of exosomal and non-exosomal miRNA in human urine","volume":"86","author":"Cheng","year":"2014","journal-title":"Kidney Int."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/7\/1529\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:41:28Z","timestamp":1760161288000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/7\/1529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,26]]},"references-count":109,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["cancers13071529"],"URL":"https:\/\/doi.org\/10.3390\/cancers13071529","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,26]]}}}