RT Journal Article
SR Electronic
T1 Metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 128
OP 137
DO 10.1136/gutjnl-2016-312432
VO 67
IS 1
A1 Julia Mayerle
A1 Holger Kalthoff
A1 Regina Reszka
A1 Beate Kamlage
A1 Erik Peter
A1 Bodo Schniewind
A1 Sandra González Maldonado
A1 Christian Pilarsky
A1 Claus-Dieter Heidecke
A1 Philipp Schatz
A1 Marius Distler
A1 Jonas A Scheiber
A1 Ujjwal M Mahajan
A1 F Ulrich Weiss
A1 Robert Grützmann
A1 Markus M Lerch
YR 2018
UL http://gut.bmj.com/content/67/1/128.abstract
AB Objective 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.Design 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.Results 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.Conclusions 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.