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Strategies to detect PDAC earlier or identify high\u2010risk 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\u2010stage PDAC. Initially, we screened previously described PanIN\u2010abundant mice, harbouring pancreatic and duodenal homeobox 1 (\n                    <jats:italic>Pdx1<\/jats:italic>\n                    )\n                    <jats:italic>\u2010Cre<\/jats:italic>\n                    , Lox\u2010STOP\u2010Lox\u2010\n                    <jats:italic>Kras<\/jats:italic>\n                    <jats:sup>G12D\/+<\/jats:sup>\n                    and floxed alleles of essential autophagy genes autophagy\u2010related 7 (\n                    <jats:italic>Atg7<\/jats:italic>\n                    ) or autophagy\u2010related 5 (\n                    <jats:italic>Atg5<\/jats:italic>\n                    ). Sera from these mice were assessed by proteomics and hits were compared to those in Lox\u2010STOP\u2010Lox\u2010\n                    <jats:italic>Kras<\/jats:italic>\n                    <jats:sup>G12D\/+<\/jats:sup>\n                    Lox\u2010STOP\u2010Lox\u2010\n                    <jats:italic>Trp53<\/jats:italic>\n                    <jats:sup>R172H\/+<\/jats:sup>\n                    <jats:italic>Pdx1\u2010Cre<\/jats:italic>\n                    (KPC) mice, which closely recapitulate human disease, and early\u2010stage (I\u2013II) PDAC patients. Levels of inter\u2010alpha\u2010trypsin 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\u2010ordinately in PDAC according to disease stage. Serum levels of C5, CFH and CD14 together constitute a novel panel for identifying PanINs and early\u2010stage PDAC with confidence, and when combined with additional screening, could help increase survival from this dismal disease.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70213","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:34:58Z","timestamp":1771482898000},"page":"1473-1493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of serum protein biomarkers for pre\u2010cancerous lesions associated with pancreatic ductal adenocarcinoma"],"prefix":"10.1002","volume":"20","author":[{"given":"Hannah","family":"Mearns","sequence":"first","affiliation":[{"name":"Cancer Research UK Scotland Institute  Glasgow UK"},{"name":"School of Cancer Sciences University of Glasgow  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn S.","family":"Long","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Institute  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Lilla","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Institute  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Hodge","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Institute  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus J. G. 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