{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:14:02Z","timestamp":1774275242712,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Iuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy Cluj-Napoca, Romania, Doctoral Research Program","award":["PCD 4789\/1 October 2022"],"award-info":[{"award-number":["PCD 4789\/1 October 2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Serum biomarker discovery in resectable pancreatic ductal adenocarcinoma (PDAC) remains a critical unmet need, as over 80% of patients present with unresectable disease. Serum proteomics offers a promising approach for identifying circulating biomarkers associated with early-stage disease; however, clinical translation has been limited by inconsistent validation and the absence of clinically relevant comparator populations. Materials and Methods: We performed a discovery-phase study using data-independent acquisition mass spectrometry-based serum proteomics in 35 patients with resectable, non-metastatic PDAC and 34 non-cancer controls without hepato-biliary-pancreatic disease. Following quality filtering (\u226580% detection threshold), 407 proteins were retained for analysis. Differential abundance was assessed using Welch\u2019s t-test with Benjamini\u2013Hochberg correction (FDR &lt; 0.01, |FC| \u2265 1.5). Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis and logistic regression with repeated stratified 5-fold cross-validation (100 repetitions) and bootstrap resampling (1000 iterations). Functional enrichment analysis was performed using g:Profiler. Results: Ninety proteins were significantly altered in PDAC (50 increased, 40 decreased). Inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) demonstrated the highest individual diagnostic performance (AUC = 0.90), followed by coagulation factor XIII A chain (F13A1; AUC = 0.89) and ferritin light chain (FTL; AUC = 0.86). Functional enrichment revealed significant overrepresentation of secretory granule lumen components (adjusted p = 0.001) and complement\/coagulation pathways (adjusted p &lt; 0.001). An enrichment-guided three-protein panel (ITIH3, F13A1, and FTL) achieved an AUC of 0.98 (95% CI: 0.95\u20131.00), with a cross-validated mean AUC of 0.96, sensitivity of 83% (95% CI: 66.4\u201393.4%), and specificity of 100% (95% CI: 89.7\u2013100%) within the discovery cohort. Conclusions: This discovery-phase study identifies a biologically coherent serum protein signature enriched for secretory granule lumen components in resectable PDAC. The three-protein panel demonstrates strong internal validation performance; however, these estimates may be optimistic due to feature selection performed prior to cross-validation. External validation in independent cohorts\u2014including chronic pancreatitis controls and parallel CA19-9 assessment\u2014will be essential to determine clinical applicability.<\/jats:p>","DOI":"10.3390\/medicina62030605","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:07:06Z","timestamp":1774271226000},"page":"605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of a Secretory Granule Lumen-Enriched Serum Protein Signature in Resectable Pancreatic Ductal Adenocarcinoma"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0960-9341","authenticated-orcid":false,"given":"Septimiu Alex","family":"Moldovan","sequence":"first","affiliation":[{"name":"Department of Surgery, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0659-8926","authenticated-orcid":false,"given":"Maria","family":"Iacobescu","sequence":"additional","affiliation":[{"name":"Department of Personalized Medicine and Rare Diseases, MedFuture\u2014Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Louis Pasteur Str., No. 4, 400347 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emil Ioan","family":"Moi\u0219","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5887-3408","authenticated-orcid":false,"given":"Florin","family":"Graur","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lumini\u0163a","family":"Furcea","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9618-9359","authenticated-orcid":false,"given":"Florin","family":"Zaharie","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-6428","authenticated-orcid":false,"given":"Andra","family":"Ciocan","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-9972","authenticated-orcid":false,"given":"Maria-Andreea","family":"Soporan","sequence":"additional","affiliation":[{"name":"Department of Personalized Medicine and Rare Diseases, MedFuture\u2014Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Louis Pasteur Str., No. 4, 400347 Cluj-Napoca, Romania"},{"name":"Department of Pharmaceutical Analysis, Faculty of Pharmacy, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Louis Pasteur Str., No. 6, 400347 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9516-0474","authenticated-orcid":false,"given":"Ioana-Ecaterina","family":"Pralea","sequence":"additional","affiliation":[{"name":"Department of Personalized Medicine and Rare Diseases, MedFuture\u2014Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Louis Pasteur Str., No. 4, 400347 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6318-3826","authenticated-orcid":false,"given":"Simona","family":"Mirel","sequence":"additional","affiliation":[{"name":"Department of Medical Devices, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Louis Pasteur Str., No. 4, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela \u015etefana","family":"Moldovan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, County Emergency Hospital, Endocrinology Clinic, Louis Pasteur Str., No. 3\u20135, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrada","family":"Seicean","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"Department of Gastroenterology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3097-707X","authenticated-orcid":false,"given":"Vlad Ionu\u021b","family":"Nechita","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"Department of Medical Informatics and Biostatistics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Louis Pasteur Str., No. 6, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0345-0993","authenticated-orcid":false,"given":"Cristina Adela","family":"Iuga","sequence":"additional","affiliation":[{"name":"Department of Personalized Medicine and Rare Diseases, MedFuture\u2014Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Louis Pasteur Str., No. 4, 400347 Cluj-Napoca, Romania"},{"name":"Department of Pharmaceutical Analysis, Faculty of Pharmacy, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Louis Pasteur Str., No. 6, 400347 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadim","family":"Al Hajjar","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cOctavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"},{"name":"Department of Surgery, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Croitorilor Str., No. 19\u201321, 400162 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1097\/SLA.0000000000001763","article-title":"Multi-Institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients with Pancreatic Adenocarcinoma","volume":"265","author":"Allen","year":"2017","journal-title":"Ann. 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