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Serum CA19-9 Is Significantly Upregulated up to 2 Years before Diagnosis with Pancreatic Cancer: Implications for Early Disease Detection
Open accessPublished version of a preprint
Abstract
PURPOSE: Biomarkers for the early detection of pancreatic cancer are urgently needed. The primary objective of this study was to evaluate whether increased levels of serum CA19-9, CA125, CEACAM1, and REG3A are present before clinical presentation of pancreatic cancer and to assess the performance of combined markers for early detection and prognosis. EXPERIMENTAL DESIGN: This nested case-control study within the UKCTOCS included 118 single and 143 serial serum samples from 154 postmenopausal women who were subsequently diagnosed with pancreatic cancer and 304 matched noncancer controls. Samples were split randomly into independent training and test sets. CA19-9, CA125, CEACAM1, and REG3A were measured using ELISA and/or CLIA. Performance of markers to detect cancers at different times before diagnosis and for prognosis was evaluated. RESULTS: At 95% specificity, CA19-9 (>37 U/mL) had a sensitivity of 68% up to 1 year, and 53% up to 2 years before diagnosis. Combining CA19-9 and CA125 improved sensitivity as CA125 was elevated (>30 U/mL) in approximately 20% of CA19-9-negative cases. CEACAM1 and REG3A were late markers adding little in combined models. Average lead times of 20 to 23 months were estimated for test-positive cases. Prediagnostic levels of CA19-9 and CA125 were associated with poor overall survival (HR, 2.69 and 3.15, respectively). CONCLUSIONS: CA19-9 and CA125 have encouraging sensitivity for detecting preclinical pancreatic cancer, and both markers can be used as prognostic tools. This work challenges the prevailing view that CA19-9 is upregulated late in the course of pancreatic cancer development.
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CA19-9 levels are elevated in blood samples collected before a diagnosis of pancreatic ductal adenocarcinoma.
“Elevated concentrations of carbohydrate antigen 19–9 (CA19–9), the only biomarker routinely used in the management of pancreatic ductal adenocarcinoma, have been shown in samples taken before diagnosis.76”
From Early detection of pancreatic cancer (2020) · cites this paper as [76]
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Metadata
- Authors
- O'Brien, D. P., Sandanayake, N. S., Jenkinson, C., Gentry-Maharaj, A., Apostolidou, S., Fourkala, E.-O., Camuzeaux, S., Blyuss, O., Gunu, R., Dawnay, A., Zaikin, A., Smith, R. C., Jacobs, I. J., Menon, U., Costello, E., Pereira, S. P., & Timms, J. F.
- Affiliations
- University College London (GB)
- The University of Sydney (AU)
- University of Liverpool (GB)
- 1Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
- University College London Hospitals NHS Foundation Trust (GB)
- University of Manchester (GB)
- Corresponding author
- Timms, John F.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2015-02-01
- Volume
- 21
- Issue
- 3
- Pages
- 622-631
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC4181906
- OpenAlex
- W2163459778
- Cited by
- 200
- References
- 52
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 10 · 2023: 11 · 2022: 24 · 2021: 24 · 2020: 33 · 2019: 12 · 2018: 23 · 2017: 17 · 2016: 11 · 2015: 8
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Pancreatic Cancer UK (RG2014_01_PERERIA, 2011 Grant)
- Cancer Research UK (A12790)
- National Institute for Health and Care Research
- National Cancer Institute (P01CA084203)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- pancreatic cancer, CA19-9, CA125, CEACAM1, REG3A, serum tumor markers, early cancer detection, preclinical cancer, combined biomarker model, prognostic factors, overall survival, lead time, postmenopausal women
- MeSH terms
- Pancreatitis-Associated Proteins, Aged, Antigens, Neoplasm, Carcinoembryonic Antigen, Humans, Middle Aged, Pancreatic Neoplasms, Prognosis, Risk Factors, Sensitivity and Specificity, Biomarkers, Tumor, Reproducibility of Results, Antigens, CD, Cell Adhesion Molecules, Up-Regulation, Case-Control Studies, CA-125 Antigen, CA-19-9 Antigen, Lectins, C-Type, Early Detection of Cancer
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