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Targeted parallel reaction monitoring, western blotting, and ELISA confirm biomarker performance, while tissue microarray analysis supports associations with cancer origin. sEV LAMB1 shows elevated plasma levels in metastatic PCa, whereas sEV Histone H4 is increased in urine of high-risk PCa, outperforming PSA in specificity and sensitivity for metastatic diagnosis, progression monitoring, and stratification.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/proteomic-identification-of-small-extracellular-vesicle-proteins-lamb1-and-histone-h4-for-prostate-cancer-diagnosis-and-risk-stratification/332160/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/proteomic-identification-of-small-extracellular-vesicle-proteins-lamb1-and-histone-h4-for-prostate-cancer-diagnosis-and-risk-stratification/332160.png","ImageObject",300,407,{"name":42,"@type":43},"Violet","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are PSA tests insufficient for prostate cancer diagnosis and risk stratification?","Question",{"text":63,"@type":64},"PSA testing has limited specificity and sensitivity, leading to missed cases and substantial overdiagnosis and overtreatment. It cannot reliably distinguish indolent from aggressive disease or accurately predict metastasis risk.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were candidate small EV protein biomarkers identified and validated?",{"text":68,"@type":64},"Candidate biomarkers were identified from PCa cell lines using label-free LC-MS/MS proteomics. They were then validated with plasma and urine samples using parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA.",{"name":70,"@type":61,"acceptedAnswer":71},"What roles do LAMB1 and Histone H4 play as biomarkers in different PCa risk groups?",{"text":72,"@type":64},"sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localized cases and controls. sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared with low-risk cases and controls.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332160,1790128006,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},4398048950312,"https://ap-avatar.wpscdn.com/avatar/400002538284de19e3c?_k=1778320343897328908","RESEARCH ARTICLE  \n[www.advancedscience.com](www.advancedscience.com)  \nProteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification  \nBairen Pang, Qi Wang, Haotian Chen, Zhihan Liu, Meng Han, Jie Gong, Liang Yue, Xuan Ding, Suying Wang, Zejun Yan, Yingzhi Chen, David Malouf, Joseph Bucci, Tiannan Guo, Cheng Zhou,* Junhui Jiang,* and Yong Li*  \nDiagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness oftissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.  \nlast decade. [2] Several studies indicate that detecting PCa at an early stage reduces mortality.[3] Despite surgery and radiation therapy that can treat localised disease, up to 30% of treated PCa patients suffer relapse and metastasis. There is no curative therapy for metastatic PCa (mPCa) and median survival is ≈1 year. The survival of PCa patients is largely related to tumour stage and grade. [4] Treatment options for different stages of PCa patients vary with risk grade.  \nA major clinical challenge in PCa management is posed by the inability of current diagnostic tests, such as serum prostatespecific antigen (PSA) testing, digital rectal examination, and histopathologic grading of tissues, to discern between indolent and aggressive disease. [5] A major knowledge gap for PCa research is the lack of suitable biomarkers for accurate diagnosis, therapeutic stratification, and predicting or monitoring metastasis. The benefits of risk stratification are to assess the overall  \n1. Introduction  \nProstate cancer (PCa) is the second most common cancer in men and nearly one and a half million men are diagnosed annually world-wide. [1] More alarming still, the percentage of patients with metastatic disease at diagnosis has increased by 25% over the  \nprogression of metastases for localised cancer, select optimal treatment options, and predict the likelihood of recurrence following definitive local therapy. Therefore, improving the screening and early diagnosis of PCa, especially metastatic disease, are of great importance in designing reasonable treatment plans and improving the prognosis of patients.  \nB. Pang, H. Chen, Z. Liu, M. Han, J. Gong, Z. Yan, Y. Chen, C. Zhou,  \nJ. Jiang  \nDepartment of Urology  \nThe First Affiliated Hospital of Ningbo University Ningbo, Zhejiang 315010, China  \nE-mail: [fyyzhoucheng@nbu.edu.cn](fyyzhoucheng@nbu.edu.cn); [fyyjiangjunhui@nbu.edu.cn](fyyjiangjunhui@nbu.edu.cn)  \nThe ORCID identification number(s) for the author(s) of this article  \ncan be found under [https://doi.org/10.1002/advs.202402509](https://doi.org/10.1002/advs.202402509)[ ](https://doi.org/10.1002/advs.202402509)© 2024 The Authors. Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution Lic","cbCaijluNUuMGOUB","https://ap.wps.com/l/cbCaijluNUuMGOUB","pdf",4842597,17,"English","# Introduction\n## Clinical challenge of PSA-based diagnosis and risk stratification\n## Need for reliable PCa biomarkers\n# Methods and validation overview\n## Label-free LC-MS/MS discovery in PCa cell lines\n## Targeted proteomics and immunoassays in plasma/urine\n## Tissue microarray confirmation","[{\"question\":\"Why are PSA tests insufficient for prostate cancer diagnosis and risk stratification?\",\"answer\":\"PSA testing has limited specificity and sensitivity, leading to missed cases and substantial overdiagnosis and overtreatment. It cannot reliably distinguish indolent from aggressive disease or accurately predict metastasis risk.\"},{\"question\":\"How were candidate small EV protein biomarkers identified and validated?\",\"answer\":\"Candidate biomarkers were identified from PCa cell lines using label-free LC-MS/MS proteomics. They were then validated with plasma and urine samples using parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA.\"},{\"question\":\"What roles do LAMB1 and Histone H4 play as biomarkers in different PCa risk groups?\",\"answer\":\"sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localized cases and controls. sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared with low-risk cases and controls.\"}]","Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification | PDF",1789997114,43]