title: Serum CA19-9 is significantly upregulated up to 2 years before diagnosis with pancreatic cancer: implications for early disease detection.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Darragh P
authors.initials: DP
authors.lastname: O'Brien
authors.affiliation: Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, United Kingdom. Kolling Institute, University of Sydney, Royal North Shore Hospital, New South Wales, Australia.
authors.forename: Neomal S
authors.initials: NS
authors.lastname: Sandanayake
authors.affiliation: The NIHR Liverpool Pancreas Biomedical Research Centre, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Jenkinson
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Sophia
authors.initials: S
authors.lastname: Apostolidou
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Evangelia-Ourania
authors.initials: EO
authors.lastname: Fourkala
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Stephane
authors.initials: S
authors.lastname: Camuzeaux
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Oleg
authors.initials: O
authors.lastname: Blyuss
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Gunu
authors.affiliation: Department of Clinical Biochemistry, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Dawnay
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Alexey
authors.initials: A
authors.lastname: Zaikin
authors.affiliation: Kolling Institute, University of Sydney, Royal North Shore Hospital, New South Wales, Australia.
authors.forename: Ross C
authors.initials: RC
authors.lastname: Smith
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom. Faculty of Medical and Human Sciences, 1.018 Core Technology Facility, University of Manchester, United Kingdom.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Jacobs
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.affiliation: The NIHR Liverpool Pancreas Biomedical Research Centre, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Eithne
authors.initials: E
authors.lastname: Costello
authors.affiliation: Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, United Kingdom. Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Pereira
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom. john.timms@ucl.ac.uk.
authors.forename: John F
authors.initials: JF
authors.lastname: Timms
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D055088:Early Detection of Cancer; D006801:Humans; D037181:Lectins, C-Type / Q000097:blood; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D000073718:Pancreatitis-Associated Proteins; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human