title: Rapid diagnosis and staging of colorectal cancer via high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy of intact tissue biopsies.
abstract: OBJECTIVE
  To develop novel metabolite-based models for diagnosis and staging in colorectal cancer (CRC) using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy.
  
  
  BACKGROUND
  Previous studies have demonstrated that cancer cells harbor unique metabolic characteristics relative to healthy counterparts. This study sought to characterize metabolic properties in CRC using HR-MAS NMR spectroscopy.
  
  
  METHODS
  Between November 2010 and January 2012, 44 consecutive patients with confirmed CRC were recruited to a prospective observational study. Fresh tissue samples were obtained from center of tumor and 5 cm from tumor margin from surgical resection specimens. Samples were run in duplicate where tissue volume permitted to compensate for anticipated sample heterogeneity. Samples were subjected to HR-MAS NMR spectroscopic profiling and acquired spectral data were imported into SIMCA and MATLAB statistical software packages for unsupervised and supervised multivariate analysis.
  
  
  RESULTS
  A total of 171 spectra were acquired (center of tumor, n = 88; 5 cm from tumor margin, n = 83). Cancer tissue contained significantly increased levels of lactate (P < 0.005), taurine (P < 0.005), and isoglutamine (P < 0.005) and decreased levels of lipids/triglycerides (P < 0.005) relative to healthy mucosa (R2Y = 0.94; Q2Y = 0.72; area under the curve, 0.98). Colon cancer samples (n = 49) contained higher levels of acetate (P < 0.005) and arginine (P < 0.005) and lower levels of lactate (P < 0.005) relative to rectal cancer samples (n = 39). In addition unique metabolic profiles were observed for tumors of differing T-stage.
  
  
  CONCLUSIONS
  HR-MAS NMR profiling demonstrates cancer-specific metabolic signatures in CRC and reveals metabolic differences between colonic and rectal cancers. In addition, this approach reveals that tumor metabolism undergoes modification during local tumor advancement, offering potential in future staging and therapeutic approaches.
authors.affiliation: *Section of Biosurgery and Surgical Technology, Department of Surgery and Cancer, Faculty of Medicine, St Mary's Hospital, Imperial College London †Section of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London ‡Centre for Pathology, Department of Medicine, Faculty of Medicine, St Mary's Hospital, Imperial College London, London, United Kingdom.
authors.forename: Reza
authors.initials: R
authors.lastname: Mirnezami
authors.forename: Beatriz
authors.initials: B
authors.lastname: Jiménez
authors.forename: Jia V
authors.initials: JV
authors.lastname: Li
authors.forename: James M
authors.initials: JM
authors.lastname: Kinross
authors.forename: Kirill
authors.initials: K
authors.lastname: Veselkov
authors.forename: Robert D
authors.initials: RD
authors.lastname: Goldin
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Ara
authors.initials: A
authors.lastname: Darzi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy / Q000379:methods*; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D003937:Diagnosis, Differential; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011446:Prospective Studies; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor