title: Validation of biomarkers that complement CA19.9 in detecting early pancreatic cancer.
abstract: OBJECTIVE
  Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer mortality. Carbohydrate antigen 19.9 (CA19.9), the only tumor marker available to detect and monitor PDAC, is not sufficiently sensitive and specific to consistently differentiate early cancer from benign disease. In this study, we aimed to validate recently discovered serum protein biomarkers for the early detection of PDAC and ultimately develop a biomarker panel that could discriminate PDAC from other benign disease better than the existing marker CA19.9.
  
  
  METHODS
  We performed a retrospective blinded evaluation of 400 serum samples collected from individuals recruited on a consecutive basis. The sample population consisted of 250 individuals with PDAC at various stages, 130 individuals with benign conditions and 20 healthy individuals. The serum levels of each biomarker were determined by ELISAs or automated immunoassay.
  
  
  RESULTS
  By randomly splitting matched samples into a training (n = 186) and validation (n = 214) set, we were able to develop and validate a biomarker panel consisting of CA19.9, CA125, and LAMC2 that significantly improved the performance of CA19.9 alone. Improved discrimination was observed in the validation set between all PDAC and benign conditions (AUCCA19.9 = 0.80 vs. AUCCA19.9+CA125+LAMC2 = 0.87; P < 0.005) as well as between early-stage PDAC and benign conditions (AUCCA19.9 = 0.69 vs. AUCCA19.9+CA125+LAMC2 = 0.76; P < 0.05) and between early-stage PDAC and chronic pancreatitis (CP; AUCCA19.9 = 0.59 vs. AUCCA19.9+CA125+LAMC2 = 0.74; P < 0.05).
  
  
  CONCLUSIONS
  The data demonstrate that a serum protein biomarker panel consisting of CA125, CA19.9, and LAMC2 is able to significantly improve upon the performance of CA19.9 alone in detecting PDAC.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Alison
authors.initials: A
authors.lastname: Chan
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Prassas
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Dimitromanolakis
authors.affiliation: University of Pittsburgh, Division of Gastroenterology, Hepatology & Nutrition, Pittsburgh, Pennsylvania.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Department of Pathology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Stefano
authors.initials: S
authors.lastname: Serra
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada. ivan.blasutig@uhn.ca.
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Blasutig
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007797:Laminin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D012372:ROC Curve; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen; C400567:LAMC2 protein, human; D007797:Laminin