Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects.

Autor:	Adam MG; Metanomics Health GmbH, Berlin, Berlin, Germany., Beyer G; Department of Medicine II, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany., Christiansen N; TrinamiX GmbH, Ludwigshafen am Rhein, Rheinland-Pfalz, Germany., Kamlage B; Metanomics Health GmbH, Berlin, Berlin, Germany., Pilarsky C; Department of Surgery, Erlangen University Hospital, Erlangen, Bayern, Germany., Distler M; Clinic and Outpatient Clinic for Visceral-, Thorax- and Vascular Surgery, Dresden University Hospital, Dresden, Sachsen, Germany., Fahlbusch T; St. Josef Hospital, Department of Surgery, Ruhr University Bochum, Bochum, Nordrhein-Westfalen, Germany., Chromik A; Askleipios Clinic Harburg, Department for General and Visceral Surgery, Asklepios Hospital Group, Hamburg, Hamburg, Germany., Klein F; Department of Surgery, Charité Universitätsmedizin Berlin Campus Charite Mitte, Berlin, Berlin, Germany., Bahra M; Department of Surgery, Charité Universitätsmedizin Berlin Campus Charite Mitte, Berlin, Berlin, Germany., Uhl W; St. Josef Hospital, Department of Surgery, Ruhr University Bochum, Bochum, Nordrhein-Westfalen, Germany., Grützmann R; Department of Surgery, Erlangen University Hospital, Erlangen, Bayern, Germany., Mahajan UM; Department of Medicine II, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany., Weiss FU; Department of Medicine A, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany., Mayerle J; Department of Medicine II, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany., Lerch MM; Department of Medicine A, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany markus.lerch@med.uni-greifswald.de.
Jazyk:	angličtina
Zdroj:	Gut [Gut] 2021 Nov; Vol. 70 (11), pp. 2150-2158. Date of Electronic Publication: 2021 Feb 04.
DOI:	10.1136/gutjnl-2020-320723
Abstrakt:	Objective: Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management. Design: We conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines. A signature to distinguish CP from controls (n=160) was identified using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry on ethylenediaminetetraacetic acid (EDTA)-plasma and validated in independent cohorts. Results: A Naive Bayes algorithm identified eight metabolites of six ontology classes. After algorithm training and computation of optimal cut-offs, classification according to the metabolic signature detected CP with an area under the curve (AUC) of 0.85 ((95% CI 0.79 to 0.91). External validation in two independent cohorts (total n=502) resulted in similar accuracy for detection of CP compared with non-pancreatic controls in EDTA-plasma (AUC 0.85 (95% CI 0.81 to 0.89)) and serum (AUC 0.87 (95% CI 0.81 to 0.95)). Conclusions: This is the first study that identifies and independently validates a metabolomic signature in plasma and serum for the diagnosis of CP in large, prospective cohorts. The results could provide the basis for the development of the first routine laboratory test for CP. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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