title: Serum metabolomic profile as a means to distinguish stage of colorectal cancer.
abstract: BACKGROUND
  Presently, colorectal cancer (CRC) is staged preoperatively by radiographic tests, and postoperatively by pathological evaluation of available surgical specimens. However, present staging methods do not accurately identify occult metastases. This has a direct effect on clinical management. Early identification of metastases isolated to the liver may enable surgical resection, whereas more disseminated disease may be best treated with palliative chemotherapy.
  
  
  METHODS
  Sera from 103 patients with colorectal adenocarcinoma treated at the same tertiary cancer center were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). Metabolic profiling was done using both supervised pattern recognition and orthogonal partial least squares-discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. The metabolomic profiles generated from each platform were compared between the following groups: locoregional CRC (N = 42); liver-only metastases (N = 45); and extrahepatic metastases (N = 25).
  
  
  RESULTS
  The serum metabolomic profile associated with locoregional CRC was distinct from that associated with liver-only metastases, based on 1H NMR spectroscopy (P = 5.10 × 10-7) and GC-MS (P = 1.79 × 10-7). Similarly, the serum metabolomic profile differed significantly between patients with liver-only metastases and with extrahepatic metastases. The change in metabolomic profile was most markedly demonstrated on GC-MS (P = 4.75 × 10-5).
  
  
  CONCLUSIONS
  In CRC, the serum metabolomic profile changes markedly with metastasis, and site of disease also appears to affect the pattern of circulating metabolites. This novel observation may have clinical utility in enhancing staging accuracy and selecting patients for surgical or medical management. Additional studies are required to determine the sensitivity of this approach to detect subtle or occult metastatic disease.
authors.affiliation: Department of Surgery, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, Canada, T2N 4N1. bathe@ucalgary.ca.
authors.forename: Farshad
authors.initials: F
authors.lastname: Farshidfar
authors.forename: Aalim M
authors.initials: AM
authors.lastname: Weljie
authors.forename: Karen
authors.initials: K
authors.lastname: Kopciuk
authors.forename: W Don
authors.initials: WD
authors.lastname: Buie
authors.forename: Anthony
authors.initials: A
authors.lastname: Maclean
authors.forename: Elijah
authors.initials: E
authors.lastname: Dixon
authors.forename: Francis R
authors.initials: FR
authors.lastname: Sutherland
authors.forename: Andrea
authors.initials: A
authors.lastname: Molckovsky
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
authors.forename: Oliver F
authors.initials: OF
authors.lastname: Bathe