{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T08:14:59Z","timestamp":1772007299611,"version":"3.50.1"},"reference-count":123,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BTM-TEC\/30087\/2017"],"award-info":[{"award-number":["PTDC\/BTM-TEC\/30087\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BTM-TEC\/30088\/2017"],"award-info":[{"award-number":["PTDC\/BTM-TEC\/30088\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Molecular diagnostics based on discovery research holds the promise of improving screening methods for prostate cancer (PCa). Furthermore, the congregated information prompts the question whether the urinary extracellular vesicles (uEV) proteome has been thoroughly explored, especially at the proteome level. In fact, most extracellular vesicles (EV) based biomarker studies have mainly targeted plasma or serum. Therefore, in this study, we aim to inquire about possible strategies for urinary biomarker discovery particularly focused on the proteome of urine EVs. Proteomics data deposited in the PRIDE archive were reanalyzed to target identifications of potential PCa markers. Network analysis of the markers proposed by different prostate cancer studies revealed moderate overlap. The recent throughput improvements in mass spectrometry together with the network analysis performed in this study, suggest that a larger standardized cohort may provide potential biomarkers that are able to fully characterize the heterogeneity of PCa. According to our analysis PCa studies based on urinary EV proteome presents higher protein coverage compared to plasma, plasma EV, and voided urine proteome. This together with a direct interaction of the prostate gland and urethra makes uEVs an attractive option for protein biomarker studies. In addition, urinary proteome based PCa studies must also evaluate samples from bladder and renal cancers to assess specificity for PCa.<\/jats:p>","DOI":"10.3390\/ijms222413605","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"13605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Extracellular Vesicle Proteome in Prostate Cancer: A Comparative Analysis of Mass Spectrometry Studies"],"prefix":"10.3390","volume":"22","author":[{"given":"Rui Miguel Marques","family":"Bernardino","sequence":"first","affiliation":[{"name":"Computational and Experimental Biology Group, Chronic Diseases Research Centre (CEDOC), NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Urology Department, Centro Hospitalar e Universit\u00e1rio de Lisboa Central, 1169-050 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3719-717X","authenticated-orcid":false,"given":"Ricardo","family":"Le\u00e3o","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Coimbra, 3000-370 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Pathology Department, Instituto Portugu\u00eas de Oncologia, 4200-072 Porto, Portugal"}]},{"given":"Luis Campos","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Urology Department, Centro Hospitalar e Universit\u00e1rio de Lisboa Central, 1169-050 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8975-5108","authenticated-orcid":false,"given":"Prashant","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, International Technology Park, Bangalore 560066, India"},{"name":"Somaiya Institute of Research and Consultancy (SIRAC), Somaiya Vidyavihar University (SVU), Vidyavihar, Mumbai 400077, India"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8535-278X","authenticated-orcid":false,"given":"Prashanth","family":"Suravajhala","sequence":"additional","affiliation":[{"name":"Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana P.O., Kollam 690525, India"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7763-3637","authenticated-orcid":false,"given":"Hans Christian","family":"Beck","sequence":"additional","affiliation":[{"name":"Centre for Clinical Proteomics, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0657-1907","authenticated-orcid":false,"given":"Ana Sofia","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, Chronic Diseases Research Centre (CEDOC), NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-2616","authenticated-orcid":false,"given":"Rune","family":"Matthiesen","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, Chronic Diseases Research Centre (CEDOC), NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bax, C., Taverna, G., Eusebio, L., Sironi, S., Grizzi, F., Guazzoni, G., and Capelli, L. (2018). Innovative Diagnostic Methods for Early Prostate Cancer Detection through Urine Analysis: A Review. Cancers, 10.","DOI":"10.3390\/cancers10040123"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer statistics, 2016","volume":"66","author":"Siegel","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","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":"CA Cancer J. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S0090-4295(96)00061-1","article-title":"Serum prostate-specific antigen and digital rectal examination for early detection of prostate cancer in a national community-based program. The Prostate Cancer Education Council","volume":"47","author":"Crawford","year":"1996","journal-title":"Urology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/bju.12854","article-title":"Guideline of guidelines: Prostate cancer screening","volume":"114","author":"Loeb","year":"2014","journal-title":"BJU Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/j.1464-410X.2012.11072.x","article-title":"Role of transrectal ultrasonography (TRUS) in focal therapy of prostate cancer: Report from a Consensus Panel","volume":"110","author":"Smeenge","year":"2012","journal-title":"BJU Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/S1470-2045(18)30569-2","article-title":"Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): A prospective, multicentre, paired diagnostic study","volume":"20","author":"Rouviere","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0140-6736(16)32401-1","article-title":"Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study","volume":"389","author":"Ahmed","year":"2017","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.eururo.2018.11.031","article-title":"Detection of Individual Prostate Cancer Foci via Multiparametric Magnetic Resonance Imaging","volume":"75","author":"Johnson","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.juro.2017.01.077","article-title":"Impact of Gleason Subtype on Prostate Cancer Detection Using Multiparametric Magnetic Resonance Imaging: Correlation with Final Histopathology","volume":"198","author":"Truong","year":"2017","journal-title":"J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/JU.0000000000002182","article-title":"Why Does Magnetic Resonance Imaging-Targeted Biopsy Miss Clinically Significant Cancer?","volume":"207","author":"Williams","year":"2021","journal-title":"J. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00345-018-2374-8","article-title":"Beyond transrectal ultrasound-guided prostate biopsies: Available techniques and approaches","volume":"37","author":"Warlick","year":"2019","journal-title":"World J. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"41.e41","DOI":"10.1016\/j.urolonc.2013.04.011","article-title":"Urine microRNAs as potential noninvasive biomarkers in urologic cancers","volume":"32","author":"Mlcochova","year":"2014","journal-title":"Urol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12620","DOI":"10.3390\/ijms140612620","article-title":"The present and future of prostate cancer urine biomarkers","volume":"14","author":"Rigau","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6835","DOI":"10.18632\/oncotarget.6899","article-title":"Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer","volume":"7","author":"Royo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1021\/pr100835s","article-title":"Quantitative analysis of the intra- and inter-individual variability of the normal urinary proteome","volume":"10","author":"Nagaraj","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ebiom.2019.06.021","article-title":"Proteomic analysis of urinary extracellular vesicles reveal biomarkers for neurologic disease","volume":"45","author":"Wang","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mora, E.M., Alvarez-Cubela, S., and Oltra, E. (2015). Biobanking of Exosomes in the Era of Precision Medicine: Are We There Yet?. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010013"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32570","DOI":"10.3402\/jev.v5.32570","article-title":"High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources","volume":"5","author":"Haraszti","year":"2016","journal-title":"J. Extracell. Vesicles"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"561571","DOI":"10.1155\/2014\/561571","article-title":"Extracellular vesicles in prostate cancer: New future clinical strategies?","volume":"2014","author":"Giusti","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/aja.2013.6","article-title":"Urinary biomarkers for prostate cancer: A review","volume":"15","author":"Hessels","year":"2013","journal-title":"Asian J. Androl."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41556-018-0040-4","article-title":"Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation","volume":"20","author":"Zhang","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Salciccia, S., Capriotti, A.L., Lagana, A., Fais, S., Logozzi, M., De Berardinis, E., Busetto, G.M., Di Pierro, G.B., Ricciuti, G.P., and Del Giudice, F. (2021). Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094367"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1586\/14789450.2014.890894","article-title":"The proteomics of prostate cancer exosomes","volume":"11","author":"Drake","year":"2014","journal-title":"Expert Rev. Proteom."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","unstructured":"Wang, Y.T., Shi, T., Srivastava, S., Kagan, J., Liu, T., and Rodland, K.D. (2020). Proteomic Analysis of Exosomes for Discovery of Protein Biomarkers for Prostate and Bladder Cancer. Cancers, 12.","DOI":"10.3390\/cancers12092335"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e12659","DOI":"10.1111\/cpr.12659","article-title":"Extracellular vesicles in urologic malignancies-Implementations for future cancer care","volume":"52","author":"Wu","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e12093","DOI":"10.1002\/jev2.12093","article-title":"Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles","volume":"10","author":"Erdbrugger","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.eururo.2015.04.039","article-title":"Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment","volume":"70","author":"Tomlins","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.juro.2010.12.032","article-title":"A multicenter study of [-2]pro-prostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng\/ml prostate specific antigen range","volume":"185","author":"Catalona","year":"2011","journal-title":"J. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1200\/JCO.2009.24.1968","article-title":"Reducing unnecessary biopsy during prostate cancer screening using a four-kallikrein panel: An independent replication","volume":"28","author":"Vickers","year":"2010","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nri855","article-title":"Exosomes: Composition, biogenesis and function","volume":"2","author":"Thery","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Martins, A.M., Ramos, C.C., Freitas, D., and Reis, C.A. (2021). Glycosylation of Cancer Extracellular Vesicles: Capture Strategies, Functional Roles and Potential Clinical Applications. Cells, 10.","DOI":"10.3390\/cells10010109"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"eaax8849","DOI":"10.1126\/sciadv.aax8849","article-title":"Mechanisms of nuclear content loading to exosomes","volume":"5","author":"Yokoi","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1080\/21541248.2016.1215283","article-title":"Biology and biogenesis of shed microvesicles","volume":"8","author":"Tricarico","year":"2017","journal-title":"Small GTPases"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1074\/mcp.M114.038273","article-title":"Glycoproteomic analysis of prostate cancer tissues by SWATH mass spectrometry discovers N-acylethanolamine acid amidase and protein tyrosine kinase 7 as signatures for tumor aggressiveness","volume":"13","author":"Liu","year":"2014","journal-title":"Mol. Cell. Proteom. MCP"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nrc2090","article-title":"Inflammation in prostate carcinogenesis","volume":"7","author":"Platz","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1038\/onc.2014.212","article-title":"Stromal fibroblast-derived miR-409 promotes epithelial-to-mesenchymal transition and prostate tumorigenesis","volume":"34","author":"Josson","year":"2015","journal-title":"Oncogene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/jcb.25611","article-title":"c-Src, Insulin-Like Growth Factor I Receptor, G-Protein-Coupled Receptor Kinases and Focal Adhesion Kinase are Enriched Into Prostate Cancer Cell Exosomes","volume":"118","author":"DeRita","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lundholm, M., Schroder, M., Nagaeva, O., Baranov, V., Widmark, A., Mincheva-Nilsson, L., and Wikstrom, P. (2014). Prostate tumor-derived exosomes down-regulate NKG2D expression on natural killer cells and CD8+ T cells: Mechanism of immune evasion. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108925"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.18632\/oncotarget.6540","article-title":"Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche","volume":"7","author":"Sanchez","year":"2016","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Min, L., Garbutt, C., Hornicek, F., and Duan, Z. (2018). The Emerging Roles and Clinical Potential of Exosomes in Cancer: Drug Resistance. Diagnostic and Therapeutic Applications of Exosomes in Cancer, Academic Press.","DOI":"10.1016\/B978-0-12-812774-2.00016-X"},{"key":"ref_49","first-page":"4331","article-title":"Expulsion of small molecules in vesicles shed by cancer cells: Association with gene expression and chemosensitivity profiles","volume":"63","author":"Shedden","year":"2003","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/pros.23005","article-title":"The presence and clinical implication of intraductal carcinoma of prostate in metastatic castration resistant prostate cancer","volume":"75","author":"Chen","year":"2015","journal-title":"Prostate"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.cell.2020.07.009","article-title":"Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers","volume":"182","author":"Hoshino","year":"2020","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3648","DOI":"10.1182\/blood-2010-10-311415","article-title":"A microRNA expression signature of osteoclastogenesis","volume":"117","author":"Sugatani","year":"2011","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/aja.2012.116","article-title":"An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions","volume":"15","author":"Zhang","year":"2013","journal-title":"Asian J. Androl."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Karlsson, T., Lundholm, M., Widmark, A., and Persson, E. (2016). Tumor Cell-Derived Exosomes from the Prostate Cancer Cell Line TRAMP-C1 Impair Osteoclast Formation and Differentiation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166284"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/nm.2753","article-title":"Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET","volume":"18","author":"Peinado","year":"2012","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/ncomms2282","article-title":"Delivery of chemotherapeutic drugs in tumour cell-derived microparticles","volume":"3","author":"Tang","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_57","first-page":"75","article-title":"A comprehensive overview of exosomes as drug delivery vehicles\u2014Endogenous nanocarriers for targeted cancer therapy","volume":"1846","author":"Johnsen","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1074\/jbc.M111.288662","article-title":"Competitive interactions of cancer cells and normal cells via secretory microRNAs","volume":"287","author":"Kosaka","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12277","DOI":"10.1038\/ncomms12277","article-title":"Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module","volume":"7","author":"Yim","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41585-020-00400-w","article-title":"Genomic and phenotypic heterogeneity in prostate cancer","volume":"18","author":"Haffner","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/(SICI)1096-9896(199611)180:3<295::AID-PATH663>3.0.CO;2-W","article-title":"Histological grade heterogeneity in multifocal prostate cancer. Biological and clinical implications","volume":"180","author":"Ruijter","year":"1996","journal-title":"J. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/PAS.0b013e3181c3ece9","article-title":"False-negative prostate needle biopsies: Frequency, histopathologic features, and follow-up","volume":"34","author":"Wolters","year":"2010","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S0022-5347(05)66086-7","article-title":"Relationship between systematic biopsies and histological features of 222 radical prostatectomy specimens: Lack of prediction of tumor significance for men with nonpalpable prostate cancer","volume":"166","author":"Noguchi","year":"2001","journal-title":"J. Urol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1001\/jama.2014.17942","article-title":"Comparison of MR\/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer","volume":"313","author":"Siddiqui","year":"2015","journal-title":"JAMA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.eururo.2015.08.052","article-title":"PI-RADS Prostate Imaging\u2014Reporting and Data System: 2015, Version 2","volume":"69","author":"Weinreb","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1056\/NEJMoa1801993","article-title":"MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis","volume":"378","author":"Kasivisvanathan","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_67","first-page":"33","article-title":"Uromodulin (Tamm-Horsfall protein): Guardian of urinary and systemic homeostasis","volume":"35","author":"Micanovic","year":"2020","journal-title":"Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc.-Eur. Ren. Assoc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/gb-2006-7-9-r80","article-title":"The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins","volume":"7","author":"Adachi","year":"2006","journal-title":"Genome Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1038\/sj.bjc.6605058","article-title":"Prostate cancer-derived urine exosomes: A novel approach to biomarkers for prostate cancer","volume":"100","author":"Nilsson","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_70","first-page":"281","article-title":"Tumor-derived exosomes as mediators of disease and potential diagnostic biomarkers","volume":"8","author":"Roberson","year":"2010","journal-title":"Cancer Biomark. Sect. A Dis. Markers"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/CCO.0b013e32835b7c81","article-title":"Tumor-cell-derived microvesicles as carriers of molecular information in cancer","volume":"25","author":"Martins","year":"2013","journal-title":"Curr. Opin. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Thery, C., Amigorena, S., Raposo, G., and Clayton, A. (2006). Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol.","DOI":"10.1002\/0471143030.cb0322s30"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1586\/epr.09.17","article-title":"Exosomes: Proteomic insights and diagnostic potential","volume":"6","author":"Simpson","year":"2009","journal-title":"Expert Rev. Proteom."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Duijvesz, D., Burnum-Johnson, K.E., Gritsenko, M.A., Hoogland, A.M., Vredenbregt-van den Berg, M.S., Willemsen, R., Luider, T., Pasa-Tolic, L., and Jenster, G. (2013). Proteomic profiling of exosomes leads to the identification of novel biomarkers for prostate cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082589"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.bbalip.2013.04.011","article-title":"Molecular lipidomics of exosomes released by PC-3 prostate cancer cells","volume":"1831","author":"Llorente","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.eururo.2014.07.035","article-title":"Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer","volume":"67","author":"Huang","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.jprot.2009.01.007","article-title":"Clinical collection and protein properties of expressed prostatic secretions as a source for biomarkers of prostatic disease","volume":"72","author":"Drake","year":"2009","journal-title":"J. Proteom."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1203\/00006450-200209000-00007","article-title":"The number of podocyte slit diaphragms is decreased in minimal change nephrotic syndrome","volume":"52","author":"Patrakka","year":"2002","journal-title":"Pediatric Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"703","DOI":"10.2217\/17435889.3.5.703","article-title":"Clearance properties of nano-sized particles and molecules as imaging agents: Considerations and caveats","volume":"3","author":"Longmire","year":"2008","journal-title":"Nanomedicine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0304-4157(85)90008-5","article-title":"The prostasome: Its secretion and function in man","volume":"822","author":"Ronquist","year":"1985","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1074\/mcp.M117.068577","article-title":"Database-augmented Mass Spectrometry Analysis of Exosomes Identifies Claudin 3 as a Putative Prostate Cancer Biomarker","volume":"16","author":"Worst","year":"2017","journal-title":"Mol. Cell. Proteom. MCP"},{"key":"ref_82","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_83","doi-asserted-by":"crossref","first-page":"e1900077","DOI":"10.1002\/prca.201900077","article-title":"MS-Based Biomarker Discovery in Bronchoalveolar Lavage Fluid for Lung Cancer","volume":"14","author":"Matthiesen","year":"2020","journal-title":"Proteomics Clin. Appl."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1021\/pr2011236","article-title":"Identification of prostate-enriched proteins by in-depth proteomic analyses of expressed prostatic secretions in urine","volume":"11","author":"Principe","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.eururo.2015.10.053","article-title":"The Proteome of Primary Prostate Cancer","volume":"69","author":"Wikstrom","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nrurol.2014.74","article-title":"Seminal plasma as a diagnostic fluid for male reproductive system disorders","volume":"11","author":"Drabovich","year":"2014","journal-title":"Nat. Rev. Urol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Zhang, X., Vos, H.R., Tao, W., and Stoorvogel, W. (2020). Proteomic Profiling of Two Distinct Populations of Extracellular Vesicles Isolated from Human Seminal Plasma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217957"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1074\/mcp.RA119.001612","article-title":"Multi-omics Biomarker Pipeline Reveals Elevated Levels of Protein-glutamine Gamma-glutamyltransferase 4 in Seminal Plasma of Prostate Cancer Patients","volume":"18","author":"Drabovich","year":"2019","journal-title":"Mol. Cell. Proteom. MCP"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/andr.12412","article-title":"Comprehensive proteomics analysis of exosomes derived from human seminal plasma","volume":"5","author":"Yang","year":"2017","journal-title":"Andrology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e1900174","DOI":"10.1002\/pmic.201900174","article-title":"Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia","volume":"19","author":"Kawahara","year":"2019","journal-title":"Proteomics"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jprot.2018.11.009","article-title":"High sensitivity proteomics of prostate cancer tissue microarrays to discriminate between healthy and cancerous tissue","volume":"197","author":"Turiak","year":"2019","journal-title":"J. Proteom."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"398","DOI":"10.2741\/4811","article-title":"Extra-cellular vesicles carry proteome of cancer hallmarks","volume":"25","author":"Carvalho","year":"2020","journal-title":"Front. Biosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"86999","DOI":"10.18632\/oncotarget.13569","article-title":"Proteomic profiling of NCI-60 extracellular vesicles uncovers common protein cargo and cancer type-specific biomarkers","volume":"7","author":"Hurwitz","year":"2016","journal-title":"Oncotarget"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1136\/jcp.2004.018077","article-title":"The role of CA125 in clinical practice","volume":"58","author":"Moss","year":"2005","journal-title":"J. Clin. Pathol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1006\/scbi.1998.0119","article-title":"The carcinoembryonic antigen (CEA) family: Structures, suggested functions and expression in normal and malignant tissues","volume":"9","author":"Hammarstrom","year":"1999","journal-title":"Semin. Cancer Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrurol.2012.258","article-title":"Aberrant PSA glycosylation\u2014A sweet predictor of prostate cancer","volume":"10","author":"Gilgunn","year":"2013","journal-title":"Nat. Rev. Urol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Scott, E., and Munkley, J. (2019). Glycans as Biomarkers in Prostate Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061389"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e2000019","DOI":"10.1002\/pmic.202000019","article-title":"Quantitative Proteomic Analysis of Global Protein Acetylation in PRRSV-Infected Pulmonary Alveolar Macrophages","volume":"21","author":"Fang","year":"2021","journal-title":"Proteomics"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1021\/acs.jproteome.0c00508","article-title":"Zirconium(IV)-IMAC Revisited: Improved Performance and Phosphoproteome Coverage by Magnetic Microparticles for Phosphopeptide Affinity Enrichment","volume":"20","author":"Govender","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41467-020-20509-1","article-title":"Data-independent acquisition method for ubiquitinome analysis reveals regulation of circadian biology","volume":"12","author":"Hansen","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1021\/acs.jproteome.0c00892","article-title":"MaxQuant.Live Enables Enhanced Selectivity and Identification of Peptides Modified by Endogenous SUMO and Ubiquitin","volume":"20","author":"Hendriks","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.21037\/tau-20-1210","article-title":"Extracellular vesicles in prostate cancer: A narrative review","volume":"10","author":"Hatano","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1074\/mcp.M111.014845","article-title":"Exosomes as biomarker enriched microvesicles: Characterization of exosomal proteins derived from a panel of prostate cell lines with distinct AR phenotypes","volume":"11","author":"Pham","year":"2012","journal-title":"Mol. Cell. Proteom. MCP"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1074\/mcp.M113.032136","article-title":"Proteomics analysis of cancer exosomes using a novel modified aptamer-based array (SOMAscan) platform","volume":"13","author":"Webber","year":"2014","journal-title":"Mol. Cell. Proteom. MCP"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Khan, S., Jutzy, J.M., Valenzuela, M.M., Turay, D., Aspe, J.R., Ashok, A., Mirshahidi, S., Mercola, D., Lilly, M.B., and Wall, N.R. (2012). Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046737"},{"key":"ref_106","first-page":"80","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. Off. J. Eur. Fed. Pharm. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00441-016-2430-x","article-title":"Function of extracellular vesicle-associated miRNAs in metastasis","volume":"365","author":"Dhondt","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jprot.2014.07.021","article-title":"From hundreds to thousands: Widening the normal human Urinome (1)","volume":"112","author":"Santucci","year":"2015","journal-title":"J. Proteom."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1586\/14789450.2015.1055324","article-title":"The human urinary exosome as a potential metabolic effector cargo","volume":"12","author":"Bruschi","year":"2015","journal-title":"Expert Rev. Proteom."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature10098","article-title":"Global quantification of mammalian gene expression control","volume":"473","author":"Schwanhausser","year":"2011","journal-title":"Nature"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Smyth, G.K. (2004). Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol., 3.","DOI":"10.2202\/1544-6115.1027"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"42961","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_114","doi-asserted-by":"crossref","first-page":"22097","DOI":"10.3402\/jev.v2i0.22097","article-title":"Exosomal ITGA3 interferes with non-cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients","volume":"2","author":"Bijnsdorp","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/S0002-9440(10)63412-8","article-title":"Heterogeneity in primary and metastatic prostate cancer as defined by cell surface CD profile","volume":"165","author":"Liu","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/1061186X.2019.1641508","article-title":"Biological characteristics of exosomes and genetically engineered exosomes for the targeted delivery of therapeutic agents","volume":"28","author":"Lin","year":"2020","journal-title":"J. Drug Target."},{"key":"ref_117","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_118","doi-asserted-by":"crossref","unstructured":"Verma, M., Lam, T.K., Hebert, E., and Divi, R.L. (2015). Extracellular vesicles: Potential applications in cancer diagnosis, prognosis, and epidemiology. BMC Clin. Pathol., 15.","DOI":"10.1186\/s12907-015-0005-5"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.1074\/jbc.C114.617662","article-title":"The alphavbeta6 integrin is transferred intercellularly via exosomes","volume":"290","author":"Fedele","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature15756","article-title":"Tumour exosome integrins determine organotropic metastasis","volume":"527","author":"Hoshino","year":"2015","journal-title":"Nature"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"14639","DOI":"10.18632\/oncotarget.7052","article-title":"Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment","volume":"7","author":"Choi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Sousa, D., Matthiesen, R., Lima, R.T., and Vasconcelos, M.H. (2020). Deep Sequencing Analysis Reveals Distinctive Non-Coding RNAs When Comparing Tumor Multidrug-Resistant Cells and Extracellular Vesicles with Drug-Sensitive Counterparts. Cancers, 12.","DOI":"10.3390\/cancers12010200"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.bbrc.2019.12.084","article-title":"The role of actinin-4 (ACTN4) in exosomes as a potential novel therapeutic target in castration-resistant prostate cancer","volume":"523","author":"Ishizuya","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13605\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:51Z","timestamp":1760169111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,19]]},"references-count":123,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413605"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413605","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,19]]}}}