{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:29:19Z","timestamp":1786537759878,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,10]]},"group-title":"Gastroenterology","reference-count":20,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NCI","award":["NCI U01CA200468"],"award-info":[{"award-number":["NCI U01CA200468"]}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108314"],"award-info":[{"award-number":["2 U01 DK108314"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["1 U01 DK126365"],"award-info":[{"award-number":["1 U01 DK126365"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108306"],"award-info":[{"award-number":["2 U01 DK108306"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108323"],"award-info":[{"award-number":["2 U01 DK108323"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["1 U01 DK126300"],"award-info":[{"award-number":["1 U01 DK126300"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108326"],"award-info":[{"award-number":["2 U01 DK108326"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108334"],"award-info":[{"award-number":["2 U01 DK108334"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108327"],"award-info":[{"award-number":["2 U01 DK108327"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108288"],"award-info":[{"award-number":["2 U01 DK108288"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108328"],"award-info":[{"award-number":["2 U01 DK108328"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108300"],"award-info":[{"award-number":["2 U01 DK108300"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["2 U01 DK108320"],"award-info":[{"award-number":["2 U01 DK108320"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>PURPOSE<\/jats:title>\n                  <jats:p>To assess the predictive performance of panel protein biomarkers as well as an established algorithm that considers repeat biomarker testing for risk prediction of PDAC among a prospective cohort of patients with New-onset diabetes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>PATIENTS AND METHODS<\/jats:title>\n                  <jats:p>A panel of protein biomarkers (CA19-9, CA125, CEA, LRG1, REG3A and TIMP1) were assayed in 6,516 serially collected pre-diagnostic plasma samples from 2,121 NOD patients from the Consortium of Chronic Pancreatitis Diabetes and Pancreatic Cancer (CPDPC)-initiated NOD study who completed the 3-year study follow-up period. The specimen set included 25 pre-diagnostic samples from the 12 PDAC cases diagnosed during study follow-up. We applied a single threshold (ST) method, which considers biomarker levels at a single time point, as well as a previously established parametrical empirical Bayes (PEB) algorithm, which considers prior biomarker measurements, with \u2018case\u2019 calls made based on pre-specified cutoffs corresponding to 1% 1-year risk. Resultant biomarker data as well as case calls were provided to the EDRN Data Management and Coordinating Center as part of a Prospective-sample-collection-Retrospective-Blinded-Evaluation (ProBE)-compliant Phase 3 biomarker validation study. Area under the Receiver Operating Characteristic Curves (AUC), sensitivity, specificity, population-level positive predictive value (PPV), and negative predictive value (NPV) are reported.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    The 3-year incidence of PDAC in the NOD cohort was 0.57%. When considering PDAC vs non-cancer controls, respective AUCs of individual protein biomarkers ranged from 0.52-0.94, with CA19-9 achieving the highest overall performance of 0.94 (95% CI: 0.86-1.00). At the pre-defined 1% 1-year risk threshold, CA19-9 yielded sensitivity of 83.3% at 97.2% specificity. Additional markers CEA, CA125, and TIMP1 demonstrated sensitivity of 33.3%, 41.7%, and 8.3%, respectively. In a subset of patients, CA19-9 first tested \u2018positive\u2019 at a median (interquartile range [IQR]) of 7 months (4 to 14 months) prior to clinical PDAC diagnosis. Of the two PDAC cases missed by CA19-9 using the ST method, one (diagnosed with stage III PDAC) was detected using the PEB\n                    <jats:sup>CA19-9<\/jats:sup>\n                    algorithm.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSION<\/jats:title>\n                  <jats:p>In the setting of adult new onset diabetes, CA19-9 is a readily available and promising biomarker that can be leveraged for earlier detection of an underlying pancreatic cancer. Additional protein biomarkers may improve sensitivity for earlier detection of PDAC among cases with low CA19-9.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.06.26359908","type":"posted-content","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:15:14Z","timestamp":1786371314000},"source":"Crossref","is-referenced-by-count":0,"title":["Assessment of impending pancreatic cancer in a cohort of new onset diabetes on basis of biomarker trajectory"],"prefix":"10.64898","author":[{"given":"Ehsan","family":"Irajizad","sequence":"first","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camden","family":"Lopez","sequence":"additional","affiliation":[{"name":"Biostatistics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, 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