title: A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics.
abstract: Timely diagnosis and classification of colorectal cancer (CRC) are hindered by unsatisfactory clinical assays. Our aim was to construct a blood-based biomarker series using a single assay, suitable for CRC detection, prognostication and staging.
  
  
  
  Serum metabolomic profiles of adenoma (N=31), various stages of CRC (N=320) and healthy matched controls (N=254) were analysed by gas chromatography-mass spectrometry (GC-MS). A diagnostic model for CRC was derived by orthogonal partial least squares-discriminant analysis (OPLS-DA) on a training set, and then validated on an independent data set. Metabolomic models suitable for identifying adenoma, poor prognosis stage II CRC and discriminating various stages were generated.
  
  
  
  A diagnostic signature for CRC with remarkable multivariate performance (R(2)Y=0.46, Q(2)Y=0.39) was constructed, and then validated (sensitivity 85%; specificity 86%). Area under the receiver-operating characteristic curve was 0.91 (95% CI, 0.87-0.96). Adenomas were also detectable (R(2)Y=0.35, Q(2)Y=0.26, internal AUROC=0.81, 95% CI, 0.70-0.92). Also of particular interest, we identified models that stratified stage II by prognosis, and classified cases by stage.
  
  
  
  Using a single assay system, a suite of CRC biomarkers based on circulating metabolites enables early detection, prognostication and preliminary staging information. External population-based studies are required to evaluate the repeatability of our findings and to assess the clinical benefits of these biomarkers.
authors: Department of Surgery, University of Calgary, Calgary, AB, Canada.|Department of Oncology, University of Calgary, Calgary, AB, Canada.
authors: Farshad
authors: F
authors: Farshidfar
authors: Department of Biological Sciences, University of Calgary, Calgary, AB, Canada.|Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.
authors: Aalim M
authors: AM
authors: Weljie
authors: Department of Mathematics and Statistics, University of Calgary, Calgary, AB, Canada.|Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, AB, Canada.
authors: Karen A
authors: KA
authors: Kopciuk
authors: Department of Medicine, University of Calgary, Calgary, AB, Canada.|Forzani and MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB, Canada.
authors: Robert
authors: R
authors: Hilsden
authors: Department of Oncology, University of Calgary, Calgary, AB, Canada.|Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, AB, Canada.
authors: S Elizabeth
authors: SE
authors: McGregor
authors: Department of Surgery, University of Calgary, Calgary, AB, Canada.
authors: W Donald
authors: WD
authors: Buie
authors: Department of Surgery, University of Calgary, Calgary, AB, Canada.
authors: Anthony
authors: A
authors: MacLean
authors: Department of Biological Sciences, University of Calgary, Calgary, AB, Canada.
authors: Hans J
authors: HJ
authors: Vogel
authors: Department of Surgery, University of Calgary, Calgary, AB, Canada.|Department of Oncology, University of Calgary, Calgary, AB, Canada.
authors: Oliver F
authors: OF
authors: Bathe
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins