title: Metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis.
abstract: Current non-invasive diagnostic tests can distinguish between pancreatic cancer (pancreatic ductal adenocarcinoma (PDAC)) and chronic pancreatitis (CP) in only about two thirds of patients. We have searched for blood-derived metabolite biomarkers for this diagnostic purpose.
  
  
  
  For a case-control study in three tertiary referral centres, 914 subjects were prospectively recruited with PDAC (n=271), CP (n=282), liver cirrhosis (n=100) or healthy as well as non-pancreatic disease controls (n=261) in three consecutive studies. Metabolomic profiles of plasma and serum samples were generated from 477 metabolites identified by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry.
  
  
  
  A biomarker signature (nine metabolites and additionally CA19-9) was identified for the differential diagnosis between PDAC and CP. The biomarker signature distinguished PDAC from CP in the training set with an area under the curve (AUC) of 0.96 (95% CI 0.93-0.98). The biomarker signature cut-off of 0.384 at 85% fixed specificity showed a sensitivity of 94.9% (95% CI 87.0%-97.0%). In the test set, an AUC of 0.94 (95% CI 0.91-0.97) and, using the same cut-off, a sensitivity of 89.9% (95% CI 81.0%-95.5%) and a specificity of 91.3% (95% CI 82.8%-96.4%) were achieved, successfully validating the biomarker signature.
  
  
  
  In patients with CP with an increased risk for pancreatic cancer (cumulative incidence 1.95%), the performance of this biomarker signature results in a negative predictive value of 99.9% (95% CI 99.7%-99.9%) (training set) and 99.8% (95% CI 99.6%-99.9%) (test set). In one third of our patients, the clinical use of this biomarker signature would have improved diagnosis and treatment stratification in comparison to CA19-9.
authors.affiliation: Department of Medicine A, University Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.|Medizinische Klinik und Poliklinik II, Klinikum der LMU München-Grosshadern, München, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Mayerle
authors.affiliation: Section for Molecular Oncology, Institut for Experimental Cancer Research (IET), UKSH, Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
authors.affiliation: Metanomics Health GmbH, Berlin, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Reszka
authors.affiliation: Metanomics Health GmbH, Berlin, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Kamlage
authors.affiliation: Metanomics Health GmbH, Berlin, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Peter
authors.affiliation: Section for Molecular Oncology, Institut for Experimental Cancer Research (IET), UKSH, Kiel, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Schniewind
authors.affiliation: metanomics GmbH, Berlin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: González Maldonado
authors.affiliation: Department of Surgery, University Hospital, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pilarsky
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery University Medicine Greifswald, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Heidecke
authors.affiliation: Metanomics Health GmbH, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schatz
authors.affiliation: Clinic and Outpatient Clinic for Visceral-, Thorax- and Vascular Surgery, Medizinische Fakultät, TU Dresden, Dresden, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Distler
authors.affiliation: Department of Medicine A, University Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
authors.forename: Jonas A
authors.initials: JA
authors.lastname: Scheiber
authors.affiliation: Department of Medicine A, University Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.|Medizinische Klinik und Poliklinik II, Klinikum der LMU München-Grosshadern, München, Germany.
authors.forename: Ujjwal M
authors.initials: UM
authors.lastname: Mahajan
authors.affiliation: Department of Medicine A, University Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
authors.forename: F Ulrich
authors.initials: FU
authors.lastname: Weiss
authors.affiliation: Department of Surgery, University Hospital, Erlangen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Grützmann
authors.affiliation: Department of Medicine A, University Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lerch
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000473:pathology; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D055088:Early Detection of Cancer / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000175:diagnosis*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor
keywords: PANCREATIC CANCER; PANCREATITIS