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This study analyzes liquid biopsies by profiling urinary small extracellular vesicle and particle proteomes from 100 subjects using LC–MS/MS. Differential expression identified 171 proteins between IDC/Crib and non-IDC/non-Crib after multiple-testing correction. Protein correlations with Gleason grade complicate interpretation; after ISUP adjustment, two proteins remained significant. Functional enrichment showed androgen response down-regulation, and overall urinary EV proteome partially reflected prostate pathology.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/profiling-of-urinary-extracellular-vesicle-protein-signatures-from-patients-with-cribriform-and-intraductal-prostate-carcinoma-in-a-cross-sectional-study/329203/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/profiling-of-urinary-extracellular-vesicle-protein-signatures-from-patients-with-cribriform-and-intraductal-prostate-carcinoma-in-a-cross-sectional-study/329203.png","ImageObject",300,407,{"name":92,"@type":93},"Sage","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are liquid biopsies like urine investigated for IDC/Crib detection?","Question",{"text":113,"@type":114},"Urine liquid biopsies avoid invasive tissue sampling and can capture protein changes in derived extracellular vesicles associated with prostate cancer initiation and progression.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What analytical approach was used to profile urinary extracellular vesicle proteins?",{"text":118,"@type":114},"The study analyzed urinary small extracellular vesicle and particle proteomes from 100 subjects using liquid chromatography coupled to high-resolution mass spectrometry (LC–MS/MS).",{"name":120,"@type":111,"acceptedAnswer":121},"Which biological pathway showed a distinct pattern in the urinary EV proteome?",{"text":122,"@type":114},"Functional enrichment based on cancer hallmark proteins revealed androgen response down-regulation in urinary EVs from IDC/Crib compared with non-IDC/non-Crib.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},329203,1790110280,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":36},687197207057,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nProfiling of urinary extracellular vesicle protein signatures from patients with cribriform and intraductal prostate carcinoma in across-sectional study  \nRui Bernardino1,2􀀍, Ana Sofia Carvalho1􀀍, Michael J. Hall1, Liliana Alves1, Ricardo Leão3, Rashid Sayyid2, Hermínia Pereira4, Hans Christian Beck5, Luís Campos Pinheiro6, Rui Henrique7,8, Neil Fleshner2 & Rune Matthiesen1􀀍  \nPrognostic tests and treatment approaches for optimized clinical care of prostatic neoplasms are an unmet need. Prostate cancer (PCa) and derived extracellular vesicles (EVs) proteome changes occur during initiation and progression of the disease. PCa tissue proteome has been previously characterized, but screening of tissue samples constitutes an invasive procedure. Consequently, we focused this study on liquid biopsies, such as urine samples. More specifically, urinary small extracellular vesicle and particles proteome profiles of 100 subjects were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC–MS/MS). We identified 171 proteins that were differentially expressed between intraductal prostate cancer/cribriform (IDC/Crib) and non-IDC/non-Crib after correction for multiple testing. However, the strong correlation between IDC/Crib and Gleason Grade complicates the disentanglement of the underlying factors driving  \nthis association. Nevertheless, even after accounting for multiple testing and adjusting for ISUP (International Society of Urological Pathology) grading, two proteins continued to exhibit significant differential expression between IDC/Crib and non-IDC/non-Crib. Functional enrichment analysis based on cancer hallmark proteins disclosed a clear pattern of androgen response down-regulation in urinary EVs from IDC/Crib compared to non-IDC/non-Crib. Interestingly, proteome differences between IDCand cribriform were more subtle, suggesting high proteome heterogeneity. Overall, the urinary EV proteome reflected partly the prostate pathology.  \nKeywords Liquid chromatography mass spectrometry, Cribriform, Intraductal prostate carcinoma, Proteomics, Urinary extracellular vesicles and particles  \nProstate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related death among men in developed countries1. Cribriform pattern (Crib) and intraductal prostate cancer (IDC) are two histological subtypes of PCa related to poor clinical outcomes and a worse prognosis, yet there are limited clinical tools for their early detection2,3. Studies that have investigated the histologic correlation between  \n1Computational and Experimental Biology Group, iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal. 2Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. 3Cuf Hospitais, Lisbon, Portugal.  \n4Department of Pathology, Centro Hospitalar E Universitário Lisboa Central, Lisbon, Portugal. 5Centre for Clinical Proteomics, Department of Clinical Biochemistry, Odense University Hospital, 5000 Odense, Denmark.  \n6Department of Urology, Centro Hospitalar e Universitário Lisboa Central, Lisbon, Portugal. 7Department of Pathology and Cancer Biology and Epigenetics Group-Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center Raquel Seruca (Porto. CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal. 8Department of Pathology and Molecular Immunology, ICBAS – School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal. 􀀍 email: [ruimmbernardino@gmail.com](ruimmbernardino@gmail.com); [ana.carvalho@nms.unl.pt](ana.carvalho@nms.unl.pt); [rune.matthiesen@nms.unl.pt](rune.matthiesen@nms.unl.pt)  \n","cbCaidXZiUrfd8Em","https://ap.wps.com/l/cbCaidXZiUrfd8Em","pdf",3255097,16,"English","# Background\n## Clinical challenges in detecting IDC/Crib\n# Study design and methods\n## Urinary EV proteome profiling using LC–MS/MS\n# Results and interpretation\n## Differential proteins and adjustment for grading\n## Functional enrichment and androgen response down-regulation\n# Conclusions\n## Urinary EV proteome reflects prostate pathology","[{\"question\":\"Why are liquid biopsies like urine investigated for IDC/Crib detection?\",\"answer\":\"Urine liquid biopsies avoid invasive tissue sampling and can capture protein changes in derived extracellular vesicles associated with prostate cancer initiation and progression.\"},{\"question\":\"What analytical approach was used to profile urinary extracellular vesicle proteins?\",\"answer\":\"The study analyzed urinary small extracellular vesicle and particle proteomes from 100 subjects using liquid chromatography coupled to high-resolution mass spectrometry (LC–MS/MS).\"},{\"question\":\"Which biological pathway showed a distinct pattern in the urinary EV proteome?\",\"answer\":\"Functional enrichment based on cancer hallmark proteins revealed androgen response down-regulation in urinary EVs from IDC/Crib compared with non-IDC/non-Crib.\"}]","Profiling of urinary extracellular vesicle protein signatures from patients with cribriform and intraductal prostate carcinoma in across-sectional study | PDF",1789983073]