title: Esophageal cancer metabolite biomarkers detected by LC-MS and NMR methods.
abstract: BACKGROUND
  Esophageal adenocarcinoma (EAC) is a rarely curable disease and is rapidly rising worldwide in incidence. Barret's esophagus (BE) and high-grade dysplasia (HGD) are considered major risk factors for invasive adenocarcinoma. In the current study, unbiased global metabolic profiling methods were applied to serum samples from patients with EAC, BE and HGD, and healthy individuals, in order to identify metabolite based biomarkers associated with the early stages of EAC with the goal of improving prognostication.
  
  
  RESULTS
  Serum metabolite profiles from patients with EAC (n = 67), BE (n = 3), HGD (n = 9) and healthy volunteers (n = 34) were obtained using high performance liquid chromatography-mass spectrometry (LC-MS) methods. Twelve metabolites differed significantly (p<0.05) between EAC patients and healthy controls. A partial least-squares discriminant analysis (PLS-DA) model had good accuracy with the area under the receiver operative characteristic curve (AUROC) of 0.82. However, when the results of LC-MS were combined with 8 metabolites detected by nuclear magnetic resonance (NMR) in a previous study, the combination of NMR and MS detected metabolites provided a much superior performance, with AUROC = 0.95. Further, mean values of 12 of these metabolites varied consistently from healthy controls to the high-risk individuals (BE and HGD patients) and EAC subjects. Altered metabolic pathways including a number of amino acid pathways and energy metabolism were identified based on altered levels of numerous metabolites.
  
  
  CONCLUSIONS
  Metabolic profiles derived from the combination of LC-MS and NMR methods readily distinguish EAC patients and potentially promise important routes to understanding the carcinogenesis and detecting the cancer. Differences in the metabolic profiles between high-risk individuals and the EAC indicate the possibility of identifying the patients at risk much earlier to the development of the cancer.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Bowers
authors.forename: Lingyan
authors.initials: L
authors.lastname: Liu
authors.forename: Siwei
authors.initials: S
authors.lastname: Wei
authors.forename: G A Nagana
authors.initials: GA
authors.lastname: Gowda
authors.forename: Zane
authors.initials: Z
authors.lastname: Hammoud
authors.forename: Daniel
authors.initials: D
authors.lastname: Raftery
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D001471:Barrett Esophagus / Q000097:blood / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods; D055088:Early Detection of Cancer / Q000379:methods; D004938:Esophageal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D055442:Metabolome; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor