title: iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance.
abstract: BACKGROUND
  The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy subjects, and to assess the effects of jaundice on biomarker performance.
  
  
  METHODS
  Isobaric tags for relative and absolute quantification were used to compare pooled serum and pancreatic juice samples from a test set of 59 and 25 subjects, respectively. Validation was undertaken in 113 independent subjects.
  
  
  RESULTS
  Candidate proteins Complement C5, inter-α-trypsin inhibitor heavy chain H3, α1-β glycoprotein and polymeric immunoglobulin receptor were elevated in cancer, as were the reference markers CA19-9 and Reg3A. Biliary obstruction had a significant effect on the performance of the markers, in particular within the PDAC group where the presence of jaundice was associated with a significant increase in the levels of all six proteins (P<0.01). Consequently, in the absence of jaundice, proteins showed reduced sensitivity for PDAC patients over benign subjects and healthy controls (HCs). Similarly, in the presence of jaundice, markers showed reduced specificity for PDAC patients over benign subjects with jaundice. Combining markers enabled improved sensitivity for non-jaundiced PDAC patients over HCs and improved specificity for jaundiced PDAC patients over jaundiced benign disease subjects.
  
  
  CONCLUSIONS
  The presence-absence of jaundice in the clinical scenario severely impacts the performance of biomarkers for PDAC diagnosis and has implications for their clinical translation.
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, Liverpool Cancer Research-UK Centre, University of Liverpool, Liverpool, UK.
authors.forename: S
authors.initials: S
authors.lastname: Tonack
authors.forename: C
authors.initials: C
authors.lastname: Jenkinson
authors.forename: T
authors.initials: T
authors.lastname: Cox
authors.forename: V
authors.initials: V
authors.lastname: Elliott
authors.forename: R E
authors.initials: RE
authors.lastname: Jenkins
authors.forename: N R
authors.initials: NR
authors.lastname: Kitteringham
authors.forename: W
authors.initials: W
authors.lastname: Greenhalf
authors.forename: V
authors.initials: V
authors.lastname: Shaw
authors.forename: C W
authors.initials: CW
authors.lastname: Michalski
authors.forename: H
authors.initials: H
authors.lastname: Friess
authors.forename: J P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: E
authors.initials: E
authors.lastname: Costello
mesh_terms: D000368:Aged; D000510:Alpha-Globulins / Q000032:analysis; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood; D003182:Complement C5 / Q000032:analysis; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D041781:Jaundice, Obstructive / Q000097:blood* / Q000150:complications; D037181:Lectins, C-Type / Q000097:blood; D008297:Male; D008875:Middle Aged; D010189:Pancreatic Juice / Q000166:cytology*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D000073718:Pancreatitis-Associated Proteins; D019056:Receptors, Polymeric Immunoglobulin / Q000032:analysis
chemical_list: C048566:A1BG protein, human; D000510:Alpha-Globulins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D003182:Complement C5; D006023:Glycoproteins; D007136:Immunoglobulins; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D019056:Receptors, Polymeric Immunoglobulin; C011877:inter-alpha-inhibitor