{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:04:31Z","timestamp":1791201871892,"version":"4.2.0"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H04923"],"award-info":[{"award-number":["22H04923"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K24608"],"award-info":[{"award-number":["23K24608"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K02693"],"award-info":[{"award-number":["24K02693"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K02885"],"award-info":[{"award-number":["25K02885"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Early detection of pancreatic cancer remains challenging, and reliable circulating biomarkers are needed to enable earlier diagnosis and improve clinical outcomes. We conducted a plasma proteomics study using the Olink Explore HT platform to identify novel biomarker candidates for early\u2010stage pancreatic cancer. The study included 42 patients with stage I\u2013II pancreatic cancer and 43 matched controls. Plasma protein levels were quantified using the Olink Proximity Extension Assay, and differential abundance was assessed using Welch's\n                    <jats:italic>t<\/jats:italic>\n                    \u2010test with correction for multiple testing. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC). Among 5419 proteins analyzed, 982 showed significant differences between cases and controls. Carboxylesterase 3 (CES3) was the most significantly decreased protein, whereas leukocyte immunoglobulin\u2010like receptor B4 (LILRB4) was the most significantly increased protein; both demonstrated excellent diagnostic performance (AUC\u2009=\u20090.91). In addition, pancreatic polypeptide (PPY) showed markedly reduced levels in patients with tumors arising in the head of the pancreas, suggesting anatomical specificity. This comprehensive Olink\u2010based proteomic analysis identifies CES3 and LILRB4 as promising plasma biomarkers for early\u2010stage pancreatic cancer and highlights PPY as informative for tumor localization. These findings provide a valuable resource for biomarker discovery and support further validation of these candidates for noninvasive early detection and risk stratification.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70637","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:00:31Z","timestamp":1784070031000},"page":"2694-2704","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Protein Biomarkers for Early Detection of Pancreatic Cancer"],"prefix":"10.1002","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0214-3649","authenticated-orcid":false,"given":"Yingsong","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Public Health Aichi Medical University School of Medicine  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-4837","authenticated-orcid":false,"given":"Masahiro","family":"Nakatochi","sequence":"additional","affiliation":[{"name":"Public Health Informatics Unit, Department of Integrated Health Sciences Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Sasado","sequence":"additional","affiliation":[{"name":"Public Health Informatics Unit, Department of Integrated Health Sciences Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itsuki","family":"Kageyama","sequence":"additional","affiliation":[{"name":"Department of Public Health Aichi Medical University School of Medicine  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5156-4880","authenticated-orcid":false,"given":"Sayo","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Public Health Aichi Medical University School of Medicine  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4799-8782","authenticated-orcid":false,"given":"Taiki","family":"Yamaji","sequence":"additional","affiliation":[{"name":"Division of Epidemiology National Cancer Center Institute for Cancer Control  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Sasahira","sequence":"additional","affiliation":[{"name":"Department of Hepato\u2010Biliary\u2010Pancreatic Medicine Cancer Institute Hospital, Japanese Foundation for Cancer Research  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Ozaka","sequence":"additional","affiliation":[{"name":"Department of Hepato\u2010Biliary\u2010Pancreatic Medicine Cancer Institute Hospital, Japanese Foundation for Cancer Research  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ishii","sequence":"additional","affiliation":[{"name":"Gastrointestinal Medical Oncology Chiba Cancer Center  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ueno","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Egawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Tokyo Metropolitan Matsuzawa Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2530-1745","authenticated-orcid":false,"given":"Yasushi","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology Sapporo Shirakaba\u2010dai Hospital  Sapporo Japan"},{"name":"Department of Gastroenterology and Hepatology Sapporo Medical University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Obata","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kinjo Gakuin University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Public Health Informatics Unit, Department of Integrated Health Sciences Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae","family":"Sasakabe","sequence":"additional","affiliation":[{"name":"Department of Public Health Aichi Medical University School of Medicine  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asahi","family":"Hishida","sequence":"additional","affiliation":[{"name":"Department of Public Health Aichi Medical University School of Medicine  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9499-9668","authenticated-orcid":false,"given":"Shogo","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Aichi Medical University  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.02.054"},{"key":"e_1_2_13_3_1","unstructured":"Cancer Statistics \u201cCancer Information Service National Cancer Center Japan \u201d."},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.4708"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2017.11.007"},{"key":"e_1_2_13_6_1","unstructured":"Foundation for Promotion of Cancer Research \u201cCancer Statistics in Japan \u201d 2025."},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000002415"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp332"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0665-2"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djw266"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2024.100561"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-023-02072-w"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2021.100168"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06563-x"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.4c00752"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyab274"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2024.0492"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-4215"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1012408"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33464"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjonc-2023-000073"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16711-w"},{"key":"e_1_2_13_23_1","first-page":"289","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini Y.","year":"1995","journal-title":"Journal of the Royal Statistical Society. Series A, Statistics in Society"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-14464-4"},{"key":"e_1_2_13_25_1","volume-title":"R Foundation for Statistical Computing","author":"R (Version 4.3.3)","year":"2024"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti525"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty890"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adx2678"},{"key":"e_1_2_13_31_1","unstructured":"National Cancer Institute \u201cThe Early Detection Research Network \u201dhttps:\/\/edrn.nci.nih.gov\/data\u2010and\u2010resources\/biomarkers\/."},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101747"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986609789071324"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2025.100887"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-1255"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.64"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0615-z"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.11.7432"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1049\/syb2.12058"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2022.170923"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05560-x"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2015.02.006"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac670"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055501"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2024.07.016"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm102"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02538-6"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/jncics\/pkac080"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.7"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704961114"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007094"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI191942"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.14.1054"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr400132j"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00566-6"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42004-025-01665-1"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70637","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70637","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70637","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:45:23Z","timestamp":1791200723000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":56,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,12,1]]}},"alternative-id":["10.1002\/ijc.70637"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70637","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]},"assertion":[{"value":"2026-01-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}