title: Urinary Peptide Analysis Differentiates Pancreatic Cancer From Chronic Pancreatitis.
abstract: Differentiation of pancreatic cancer (PCA) from chronic pancreatitis (CP) is challenging. We searched for peptide markers in urine to develop a diagnostic peptide marker model.
  
  
  
  Capillary electrophoresis-mass spectrometry was used to search for peptides in urine of patients with PCA (n = 39) or CP (n = 41). Statistical different peptides were included in a peptide multimarker model. Peptide markers were sequence identified and validated by immunoassay and immunohistochemistry (IHC).
  
  
  
  Applied to a validation cohort of 54 patients with PCA and 52 patients with CP, the peptide model correctly classified 47 patients with PCA and 44 patients with CP (area under the curve, 0.93; 87% sensitivity; 85% specificity). All 5 patients with PCA with concomitant CP were classified positive. Urine proteome analysis outperformed carbohydrate antigen 19-9 (area under the curve, 0.84) by a 15% increase in sensitivity at the same specificity. From 99 healthy subjects, only four were misclassified. Fetuin-A was the most prominent peptide marker source for PCA as verified by immunoassay and IHC. In silico protease mapping of the peptide markers' terminal sequences pointed to increased meprin-A activity in PCA, which in IHC was associated with neoangiogenesis.
  
  
  
  Urinary proteome analysis differentiates PCA from CP and may serve as PCA screening tool.
authors.affiliation: From the *Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School; and †Mosaiques Diagnostics GmbH, Hannover, Germany; ‡Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; §Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Cardiovascular and Metabolic Disease; and ∥Université Toulouse III Paul-Sabatier, Toulouse, France; ¶Department of Gastroenterology, University of Leipzig, Leipzig; and #Department of Visceral Surgery, Hannover Medical School, Hannover, Germany; **Plateau de Protéomique des Liquides Biologiques, Institute of Cardiovascular and Metabolic Disease, Toulouse, France; and ††Department of Internal Medicine I, Medical University Hospital, Tübingen; and ‡‡Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schönemeier
authors.forename: Jochen
authors.initials: J
authors.lastname: Metzger
authors.forename: Julie
authors.initials: J
authors.lastname: Klein
authors.forename: Holger
authors.initials: H
authors.lastname: Husi
authors.forename: Birgit
authors.initials: B
authors.lastname: Bremer
authors.forename: Nina
authors.initials: N
authors.lastname: Armbrecht
authors.forename: Mohammed
authors.initials: M
authors.lastname: Dakna
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.forename: Jonas
authors.initials: J
authors.lastname: Rosendahl
authors.forename: Johannes
authors.initials: J
authors.lastname: Wiegand
authors.forename: Mark
authors.initials: M
authors.lastname: Jäger
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Breuil
authors.forename: Ruben R
authors.initials: RR
authors.lastname: Plentz
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.forename: Korbinian
authors.initials: K
authors.lastname: Brand
authors.forename: Florian
authors.initials: F
authors.lastname: Kühnel
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Tim O
authors.initials: TO
authors.lastname: Lankisch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine*; D003937:Diagnosis, Differential; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D008666:Metalloendopeptidases / Q000032:analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000652:urine*; D050500:Pancreatitis, Chronic / Q000175:diagnosis / Q000652:urine*; D010455:Peptides / Q000652:urine*; D012372:ROC Curve; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis
chemical_list: D015415:Biomarkers; D010455:Peptides; D060749:alpha-2-HS-Glycoprotein; D008666:Metalloendopeptidases; C053833:meprin A