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The study identifies serum proteins linked to pancreatic intraepithelial neoplasms (PanINs) and early-stage PDAC using genetically engineered mice and PDAC patient samples. Proteomics screening of PanIN-abundant models and comparison with KPC mice, plus validation in patients, shows coordinated increases in ITIH3, C5, CFB/CFH, and CD14 by disease stage. C5, CFH, and CD14 together form a confidence-based serum panel for detecting PanINs and early PDAC.",{"@graph":69,"@context":122},[70,84,105],{"@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/identification-of-serum-protein-biomarkers-for-pre-cancerous-lesions-associated-with-pancreatic-ductal-adenocarcinoma/345537/",{"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/identification-of-serum-protein-biomarkers-for-pre-cancerous-lesions-associated-with-pancreatic-ductal-adenocarcinoma/345537.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is early detection of PDAC clinically important?","Question",{"text":112,"@type":113},"Early-stage PDAC is often asymptomatic, causing most diagnoses to occur at later stages. This contributes to poor survival, motivating noninvasive early-detection biomarkers.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were the candidate serum biomarkers identified?",{"text":117,"@type":113},"The study screened PanIN-abundant genetically engineered mice using proteomics and compared the findings with KPC mice that recapitulate human disease, then validated the results in early-stage (I–II) PDAC patients.",{"name":119,"@type":110,"acceptedAnswer":120},"Which serum proteins form the proposed biomarker panel for PanINs and early-stage PDAC?",{"text":121,"@type":113},"The study reports that complement C5, complement factor H (CFH), and the monocyte differentiation antigen CD14 together form a novel panel, with levels increasing with disease stage.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},345537,1790259731,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Identiﬁcation of serum protein biomarkers for  \npre-cancerous lesions associated with pancreatic ductaladenocarcinoma  \nHannah Mearns 1,2, Jaclyn S. Long 1, Sergio Lilla 1, Kelly Hodge 1, Marcus J. G. W. Ladds 1,*, Colin Nixon 1, Paula Fernndez-Palanca 1, Sara Zanivan 1,2,†, Pilar Acedo3, Stephen P. Pereira3 and Kevin M. Ryan 1,2   \n1 Cancer Research UK Scotland Institute, Glasgow, UK  \n2 School of Cancer Sciences, University of Glasgow, UK  \n3 Institute for Liver and Digestive Health, Royal Free Hospital Campus, University College London (UCL), UK  \nKeywords  \nautophagy; biomarker; early detection; mice; pancreatic ductal adenocarcinoma;  \npancreatic intraepithelial neoplasia; proteomics; serum  \nCorrespondence  \nK. M. Ryan, Cancer Research UK Scotland Institute, School of Cancer Sciences, University of Glasgow. Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK Tel: +441413303655  \nE-mail: [kevin.ryan@glasgow.ac.uk](kevin.ryan@glasgow.ac.uk)  \nPresent address  \n*AstraZeneca, Cambridge, UK †Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA  \n(Received 10 March 2025, revised 24  \nSeptember 2025, accepted 21 January 2026, available online 19 February 2026)  \ndoi:10 . 1002/1878-0261 .70213  \nPancreatic ductal adenocarcinoma (PDAC) has poor prognosis as early-stage asymptomaticity leads to late-stage diagnoses. Strategies to detect PDAC earlier or identify high-risk individuals are therefore paramount. Here, we report results from genetically engineered mice and PDAC patients that identify serum proteins associated with pancreatic intraepithelial neoplasms (PanINs), the most common PDAC precursor, and early-stage PDAC. Initially, we screened previously described PanIN-abundant mice, harbouring pancreatic and duodenal homeobox 1 (Pdx1)-Cre, Lox-STOP-Lox-KrasG12D/+ and ﬂoxed alleles of essential autophagy genes autophagy-related 7 (Atg7) or autophagy-related 5 (Atg5) . Sera from these mice were assessed by proteomics and hits were compared to those in Lox-STOP-Lox-KrasG12D/+ Lox-STOP-Lox-Trp53R172H/+ Pdx1-Cre (KPC) mice, which closely recapitulate human disease, and early-stage (I–II) PDAC patients. Levels of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) were signiﬁcantly elevated in all three screens, with complement C5, complement factors B and H (CFB/CFH), and monocyte differentiation antigen CD14 increased in KPC mice and PDAC patients; and all were signiﬁcantly increased co-ordinately in PDAC according to disease stage. Serum levels of C5, CFH and CD14 together constitute a novel panel for identifying PanINs and early-stage PDAC with conﬁdence, and when combined with additional screening, could help increase survival from this dismal disease.  \n1. Introduction  \nDespite substantial advances in cancer research, there remains a large clinical unmet need for pancreatic  \ncancer patients, around 95% of whom present with pancreatic ductal adenocarcinoma (PDAC) . The unmet  \nAbbreviations  \nANOVA, Analysis of variance; ATG, Autophagy-related; C5, Complement C5; CD14, Monocyte differentiation antigen CD14; CFB, Complement factor B; CFH, Complement factor H; CPTAC, Clinical proteomic tumour analysis consortium; ECM, Extracellular matrix; GEMM, Genetically engineered mouse model; IHC, Immunohistochemistry; ITIH3, Inter-alpha-trypsin inhibitor heavy chain H3; KPC, KrasG12D/+ Trp53R172H/+ Pdx1-Cre; MS, Mass spectrometry; PanIN, Pancreatic intraepithelial neoplasia; PDAC, Pancreatic ductaladenocarcinoma; UALCAN, University of Alabama at Birmingham Cancer data analysis portal.  \nMolecular Oncology 20 (2026) 1473–1493 ª 2026 The Author(s) . Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n1473  \nSerum protein biomarkers linked to ","cbCaiq0TayRYb8hz","https://ap.wps.com/l/cbCaiq0TayRYb8hz","pdf",3323757,21,"English","# Introduction\n## Unmet clinical need and rationale for early detection\n## Limitations of existing biomarkers (e.g., CA19-9)\n## Role and detectability of PanINs","[{\"question\":\"Why is early detection of PDAC clinically important?\",\"answer\":\"Early-stage PDAC is often asymptomatic, causing most diagnoses to occur at later stages. This contributes to poor survival, motivating noninvasive early-detection biomarkers.\"},{\"question\":\"How were the candidate serum biomarkers identified?\",\"answer\":\"The study screened PanIN-abundant genetically engineered mice using proteomics and compared the findings with KPC mice that recapitulate human disease, then validated the results in early-stage (I–II) PDAC patients.\"},{\"question\":\"Which serum proteins form the proposed biomarker panel for PanINs and early-stage PDAC?\",\"answer\":\"The study reports that complement C5, complement factor H (CFH), and the monocyte differentiation antigen CD14 together form a novel panel, with levels increasing with disease stage.\"}]","Identification of Serum Protein Biomarkers for Pre-cancerous Lesions Associated with Pancreatic Ductal Adenocarcinoma | PDF",1790058019,53]