title: Metabolomics approaches in pancreatic adenocarcinoma: tumor metabolism profiling predicts clinical outcome of patients.
abstract: Pancreatic adenocarcinomas (PAs) have very poor prognoses even when surgery is possible. Currently, there are no tissular biomarkers to predict long-term survival in patients with PA. The aims of this study were to (1) describe the metabolome of pancreatic parenchyma (PP) and PA, (2) determine the impact of neoadjuvant chemotherapy on PP and PA, and (3) find tissue metabolic biomarkers associated with long-term survivors, using metabolomics analysis.
  
  
  
  1H high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy using intact tissues was applied to analyze metabolites in PP tissue samples (n = 17) and intact tumor samples (n = 106), obtained from 106 patients undergoing surgical resection for PA.
  
  
  
  An orthogonal partial least square-discriminant analysis (OPLS-DA) showed a clear distinction between PP and PA. Higher concentrations of myo-inositol and glycerol were shown in PP, whereas higher levels of glucose, ascorbate, ethanolamine, lactate, and taurine were revealed in PA. Among those metabolites, one of them was particularly obvious in the distinction between long-term and short-term survivors. A high ethanolamine level was associated with worse survival. The impact of neoadjuvant chemotherapy was higher on PA than on PP.
  
  
  
  This study shows that HRMAS NMR spectroscopy using intact tissue provides important and solid information in the characterization of PA. Metabolomics profiling can also predict long-term survival: the assessment of ethanolamine concentration can be clinically relevant as a single metabolic biomarker. This information can be obtained in 20 min, during surgery, to distinguish long-term from short-term survival.
authors.affiliation: ICube, UMR 7357 University of Strasbourg/CNRS, Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Battini
authors.affiliation: ICube, UMR 7357 University of Strasbourg/CNRS, Strasbourg, France.|Department of Visceral Surgery and Transplantation, Hautepierre Hospital, University Hospitals of Strasbourg, Strasbourg, France.|FMTS, Faculty of Medicine, Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Faitot
authors.affiliation: ICube, UMR 7357 University of Strasbourg/CNRS, Strasbourg, France.|FMTS, Faculty of Medicine, Strasbourg, France.|Department of Biophysics and Nuclear Medicine, Hautepierre Hospital, University Hospitals of Strasbourg, 1, Avenue Molière, Strasbourg, Cedex, 67098, France.
authors.forename: A
authors.initials: A
authors.lastname: Imperiale
authors.affiliation: Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA.|Computer Engineering Department, Bilkent University, Ankara, Turkey.
authors.forename: A E
authors.initials: AE
authors.lastname: Cicek
authors.affiliation: ICube, UMR 7357 University of Strasbourg/CNRS, Strasbourg, France.|FMTS, Faculty of Medicine, Strasbourg, France.|Department of Biophysics and Nuclear Medicine, Hautepierre Hospital, University Hospitals of Strasbourg, 1, Avenue Molière, Strasbourg, Cedex, 67098, France.
authors.forename: C
authors.initials: C
authors.lastname: Heimburger
authors.affiliation: Department of Pathology, Hautepierre Hospital, University Hospitals of Strasbourg, Strasbourg, France.
authors.forename: G
authors.initials: G
authors.lastname: Averous
authors.affiliation: Department of Visceral Surgery and Transplantation, Hautepierre Hospital, University Hospitals of Strasbourg, Strasbourg, France.
authors.forename: P
authors.initials: P
authors.lastname: Bachellier
authors.affiliation: ICube, UMR 7357 University of Strasbourg/CNRS, Strasbourg, France. Izzie.Jacques.NAMER@chru-strasbourg.fr.|FMTS, Faculty of Medicine, Strasbourg, France. Izzie.Jacques.NAMER@chru-strasbourg.fr.|Department of Biophysics and Nuclear Medicine, Hautepierre Hospital, University Hospitals of Strasbourg, 1, Avenue Molière, Strasbourg, Cedex, 67098, France. Izzie.Jacques.NAMER@chru-strasbourg.fr.
authors.forename: I J
authors.initials: IJ
authors.lastname: Namer
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D016002:Discriminant Analysis; D019856:Ethanolamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D017741:Survivors / Q000706:statistics & numerical data; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019856:Ethanolamine
keywords: Biomarker; HRMAS; Long-term survival; Metabolomics; NMR; Pancreatic adenocarcinoma