Z Gastroenterol 2014; 52 - FV35
DOI: 10.1055/s-0034-1386009

Metabolic biomarkers to differentiate pancreatic ductal adenocarcinoma and chronic pancreatitis

J Mayerle 1, H Kalthoff 2, R Reszka 3, B Kamlage 4, E Peter 4, B Schniewind 2, S González Maldonado 4, V Liebenberg 3, C Pilarsky 5, P Schatz 3, JA Scheiber 1, FU Weiss 1, R Grützmann 5, MM Lerch 1
  • 1Universitätsmedizin, Ernst-Moritz-Arndt-Universität Greifswald, Klinik für Innere Medizin A, Greifswald, Germany
  • 2UKSH, Campus Kiel, Kiel, Germany, Institut for Experimental Cancer Research (IET), Section for Molecular Oncology, Kiel, Germany
  • 3Metanomics Health GmbH, Berlin, Germany, Berlin, Germany
  • 4metanomics GmbH, Berlin, Germany, Berlin, Germany
  • 5University Hospital, Carl Gustav Carus, Clinic and Outpatient Clinic for Visceral-, Thorax- and Vascular Surgery, Dresden, Germany

Background: Current non-invasive diagnostic tests can distinguish between pancreatic cancer (PDAC) and chronic pancreatitis (CP) in only about two thirds of patients.

Objectives: To identify a panel of plasma metabolite biomarkers for this diagnostic purpose.

Methods: For a case-control study in three tertiary referral centres 914 subjects were prospectively recruited with either pancreatic cancer (n = 271), chronic pancreatitis (n = 282), liver cirrhosis (n = 100), or healthy as well as non-pancreatic disease controls (n = 261). An initial exploratory study (n = 201) was followed by a multicentre training study (n = 474; training set) and a third testing set (n = 239). Metabolomic profiles of plasma and serum samples were generated by high quality polar and lipid gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) identifying 477 metabolites.

Results: A consistent multimarker 10-metabolite panel (including sphingomyelin and ceramide and CA19 – 9) for the differential diagnosis of pancreatic cancer vs. chronic pancreatitis was identified by Elastic Net providing an area under the curve (AUC) of 0.96 [95% CI 0.93 – 0.98]. The panel was successfully validated on test data with an AUC of 0.94 [95% CI 0.91, 0.97]. With a fixed specificity for PDAC of 85% in the trainings data set resulted in a cut-off of 0.384, a sensitivity of 94.9% [95% CI 87.0%-97.0%%]. Using the same cut-off, a sensitivity of 89.9% [95% CI 81.0 – 95.5%] and a specificity of 91.9% [95% CI 82.8 – 96.4%] for the test set were reached. Assuming an estimated incidence of 1.95% for pancreatic cancer in a CP population negative predictive values of 99.9% [95% CI 99.7 – 99.93%] (training set) and 99.8% [95% CI 99.6 – 99.9%] (test set) were observed.

Conclusion: These results indicate that a plasma metabolite biomarker panel can be used to accurately distinguish (on the basis of a high negative predictive value (NPV) between PDAC and CP. They also permit the development of a most promising diagnostic plasma biomarker assay for the detection pancreatic cancer in high risk cohorts.

Pankreaskarzinom

Donnerstag, 18. September 2014/15:00 – 16:30/Saal Ismar Boas