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Whether small extracellular vesicles (sEVs) can reflect bladder cancer molecular subtypes is unknown. Whole transcriptome RNA sequencing was performed on FFPE tumour tissues and sEVs from matched tissue explants, urine and plasma. sEVs were isolated by size-exclusion chromatography and characterized by electron microscopy, nano flow cytometry and western blots. Concordance was seen between FFPE tissue and tissue-derived sEVs. Urine sEVs were luminal while plasma sEVs were Ba/Sq, independent of the matched tissue subtype.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/tumour-tissue-derived-small-extracellular-vesicles-reflect-molecular-subtypes-of-bladder-cancer/330044/",{"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/tumour-tissue-derived-small-extracellular-vesicles-reflect-molecular-subtypes-of-bladder-cancer/330044.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Can small extracellular vesicles reflect bladder cancer molecular subtypes?","Question",{"text":113,"@type":114},"Tumour tissue-derived sEVs showed good concordance with FFPE tumour tissue molecular subtype classification, supporting their potential to reflect molecular subtypes.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were sEVs obtained and characterized in the study?",{"text":118,"@type":114},"sEVs were separated using size-exclusion chromatography and characterized with transmission electron microscopy, nano flow cytometry, and western blots.",{"name":120,"@type":111,"acceptedAnswer":121},"Do urine and plasma sEVs match the molecular subtypes of their matched tumour tissues?",{"text":122,"@type":114},"Urine sEVs were classified as the luminal subtype and plasma sEVs as the Ba/Sq subtype regardless of the molecular subtypes indicated by their matched FFPE tumour tissue.","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},330044,1790122369,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"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":146,"preview_page_count":4},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","DOI: 10.1002/jev2.12402  \nRESEARCH ARTICLE  \nTumour tissue-derived small extracellular vesicles reflect molecular subtypes of bladder cancer  \nLiang Dong􀀃, 􀀄   Mingxiao Feng􀀄   Morgan D. Kuczler􀀄  Kengo Horie􀀄, 􀀅   \nChi-Ju Kim􀀄  Zehua Ma􀀃  Kara Lombardo􀀄  Heather Lyons􀀄  Sarah R. Amend􀀄  Max Kates􀀄  Trinity J. Bivalacqua􀀆  David McConkey􀀄  Wei Xue􀀃  Woonyoung Choi􀀄 Kenneth J. Pienta􀀄  \n1Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China  \n2The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA  \n3Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan  \n4Division of Urology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA  \nCorrespondence  \nLiang Dong and Wei Xue  \nDepartment of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.  \nEmail: [drdongliang@126.com](drdongliang@126.com) and [uroxuewei@163.com](uroxuewei@163.com)  \nWoonyoung Choi  \nThe Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, [USA. Email:](USA. Email: wchoi16@jhmi.edu)[ wchoi16@jhmi.edu](USA. Email: wchoi16@jhmi.edu)  \nFunding information  \nNational Natural Science Foundation of China, Grant/Award Numbers: 82103485, 82227801; Innovative Research Team of High-level Local University in Shanghai; Japan Society for the Promotion of Science, Grant/Award Number:  \n19K18555; Basic Science Research Program through the National Research Foundation of Korea  \nAbstract  \nmRNA-based molecular subtypes have implications for bladder cancer prognosis and clinical benefit from certain therapies. Whether small extracellular vesicles (sEVs) can reflect bladder cancer molecular subtypes is unknown. We performed whole transcriptome RNA sequencing for formalin fixed paraffin embedded (FFPE) tumour tissues and sEVs separated from matched tissue explants, urine and plasma in patients with bladder cancer. sEVs were separated using size-exclusion chromatography, and characterized by transmission electron microscopy, nano flow cytometry and western blots, respectively. High yield of sEVs were obtained using approximately 1 g of tissue, incubated with media for 30 min. FFPE tumour tissue and tumour tissue-derived sEVs demonstrated good concordance in molecular subtype classification. All urinary sEVs were classified as luminal subtype, while all plasma sEVs were classified as Ba/Sq subtype, regardless of the molecular subtypes indicated by their matched FFPE tumour tissue. The comparison within urine sEVs, which may exclude the sample type specific background, could pick up the different biology between NMIBC and MIBC, as well as the signature genes related to molecular subtypes. Four candidate sEV-related bladder cancer-specific mRNA biomarkers, FAM71E2, OR4K5, FAM138F and KRTAP26-1, were identified by analysing matched urine sEVs, tumour tissue derived sEVs, and adjacent normal tissue derived sEVs. Compared to sEVs separated from biofluids, tissue-derived sEVs may reflect more tissue-or disease-specific biological features. Urine sEVs are promising biomarkers to be used for liquid biopsy-based molecular subtype classification, but the current algorithm needs to be modified/adjusted. Future work is needed to validate the four new bladder cancer-specific biomarkers in large cohorts.  \nKEYWORDS  \nbladder cancer, extracellular vesicles, liquid biopsy, molecular subtype, tissue derived EV  \nLiang Dong and Mingxiao Feng contributed equally.  \nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.  \n©2024The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Soci","cbCais7YL7W7MIdC","https://ap.wps.com/l/cbCais7YL7W7MIdC","pdf",2888560,13,"English","# Introduction\n## Bladder cancer epidemiology and treatment\n## Molecular subtypes and consensus classification","[{\"question\":\"Can small extracellular vesicles reflect bladder cancer molecular subtypes?\",\"answer\":\"Tumour tissue-derived sEVs showed good concordance with FFPE tumour tissue molecular subtype classification, supporting their potential to reflect molecular subtypes.\"},{\"question\":\"How were sEVs obtained and characterized in the study?\",\"answer\":\"sEVs were separated using size-exclusion chromatography and characterized with transmission electron microscopy, nano flow cytometry, and western blots.\"},{\"question\":\"Do urine and plasma sEVs match the molecular subtypes of their matched tumour tissues?\",\"answer\":\"Urine sEVs were classified as the luminal subtype and plasma sEVs as the Ba/Sq subtype regardless of the molecular subtypes indicated by their matched FFPE tumour tissue.\"}]","Tumour tissue-derived small extracellular vesicles reflect molecular subtypes of bladder cancer | PDF",1789986691,33]