title: Prediagnostic serum biomarkers as early detection tools for pancreatic cancer in a large prospective cohort study.
abstract: BACKGROUND
  The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools.
  
  
  METHODS
  Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).
  
  
  RESULTS
  The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone.
  
  
  CONCLUSIONS
  Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Nolen
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Denise
authors.initials: D
authors.lastname: Prosser
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Liudmila
authors.initials: L
authors.lastname: Velikokhatnaya
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America; Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Lomakin
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Ob/Gyn, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Lokshin
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood; D015331:Cohort Studies; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis*; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D053244:Osteoprotegerin; D053495:Osteopontin
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