{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:34:29Z","timestamp":1779168869176,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pancreatic Cancer UK"},{"name":"Mayor of Gedling\u2019s Charitable Fund for Research in Pancreatic Cancer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Poor survival outcomes in periampullary cancer highlight the need for improvement in biomarkers and the development of novel therapies. Redox proteins, including the thioredoxin system, play vital roles in cellular antioxidant systems. Methods: In this retrospective study, thioredoxin (Trx), thioredoxin-interacting protein (TxNIP), and thioredoxin reductase (TrxR) protein expression was assessed in 85 patients with pancreatic ductal adenocarcinoma (PDAC) and 145 patients with distal bile duct or ampullary carcinoma using conventional immunohistochemistry. Results: In patients with PDAC, high cytoplasmic TrxR expression was significantly associated with lymph node metastasis (p = 0.033). High cytoplasmic and nuclear Trx expression was significantly associated with better overall survival (p = 0.018 and p = 0.006, respectively), and nuclear Trx expression remained significant in multivariate Cox regression analysis (p &lt; 0.0001). In distal bile duct and ampullary carcinomas, high nuclear TrxR expression was associated with vascular (p = 0.001) and perineural (p = 0.021) invasion, and low cytoplasmic TxNIP expression was associated with perineural invasion (p = 0.025). High cytoplasmic TxNIP expression was significantly associated with better overall survival (p = 0.0002), which remained significant in multivariate Cox regression analysis (p = 0.013). Conclusions: These findings demonstrate the prognostic importance of Trx system protein expression in periampullary cancers.<\/jats:p>","DOI":"10.3390\/diseases12100227","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T10:41:47Z","timestamp":1727174507000},"page":"227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Thioredoxin System Protein Expression in Carcinomas of the Pancreas, Distal Bile Duct, and Ampulla in the United Kingdom"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1674-8016","authenticated-orcid":false,"given":"Khaled S.","family":"Al-Hadyan","sequence":"first","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, University Park, Nottingham NG7 2RD, UK"},{"name":"Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-6048","authenticated-orcid":false,"given":"Sarah J.","family":"Storr","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, University Park, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3351-6460","authenticated-orcid":false,"given":"Abed M.","family":"Zaitoun","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, Nottingham University Hospitals NHS Trust, Queen\u2019s Medical Centre, Nottingham NG7 2UH, UK"},{"name":"National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen\u2019s Medical Centre, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1187-5796","authenticated-orcid":false,"given":"Dileep N.","family":"Lobo","sequence":"additional","affiliation":[{"name":"MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen\u2019s Medical Centre, Nottingham NG7 2UH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2810-2338","authenticated-orcid":false,"given":"Stewart G.","family":"Martin","sequence":"additional","affiliation":[{"name":"Nottingham Breast Cancer Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, University Park, Nottingham NG7 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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