title: Urinary Metabotyping of Hepatocellular Carcinoma in a UK Cohort Using Proton Nuclear Magnetic Resonance Spectroscopy.
abstract: BACKGROUND
  Discriminatory metabolic profiles have been described in urinary1H nuclear magnetic resonance (NMR) spectroscopy studies of African patients with hepatocellular carcinoma (HCC). This study aimed to assess similarities in a UK cohort, where there is a greater etiological diversity.
  
  
  METHODS
  Urine from cirrhosis and HCC patients was analyzed using a 600 MHz1H NMR system. Multivariate analysis and median group MR spectra comparison identified metabolite alterations between groups. Metabolite identification was achieved through literature reference and statistical total correlation spectroscopy. Diagnostic accuracy was compared to serum alpha-fetoprotein (AFP).
  
  
  RESULTS
  Of the 52 patients recruited, 13 samples from HCC and 25 from cirrhosis patients were selected. At 200 IU mL-1, diagnostic sensitivity of AFP was 27%. Multivariate analysis of urinary spectra generated diagnostic models with a sensitivity/specificity of 53.6%/96%. p-Cresol sulfate (P= 0.04), creatinine (P= 0.03), citrate (P= 0.21) and hippurate (P= 0.52) were reduced in the HCC patients. Carnitine (P= 0.31) and formate (P= 0.44) were elevated.
  
  
  CONCLUSIONS
  Diagnostic sensitivity was lower than previous African studies, but still outperformed serum AFP. Reduced creatinine, citrate and hippurate and elevated carnitine are comparable with the African studies. p-Cresol sulfate alteration is a novel finding and may indicate an altered sulfonation capacity of the liver in patients with HCC.
authors.affiliation: Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, South Wharf Road, London W2 1NY, United Kingdom.
authors.forename: Mohamed I F
authors.initials: MI
authors.lastname: Shariff
authors.affiliation: Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, South Wharf Road, London W2 1NY, United Kingdom.
authors.forename: Jin U
authors.initials: JU
authors.lastname: Kim
authors.affiliation: Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, South Wharf Road, London W2 1NY, United Kingdom.
authors.forename: Nimzing G
authors.initials: NG
authors.lastname: Ladep
authors.affiliation: Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, South Wharf Road, London W2 1NY, United Kingdom; Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Mary M E
authors.initials: MM
authors.lastname: Crossey
authors.affiliation: Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, South Wharf Road, London W2 1NY, United Kingdom.
authors.forename: Larry K
authors.initials: LK
authors.lastname: Koomson
authors.affiliation: Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, South Wharf Road, London W2 1NY, United Kingdom.
authors.forename: Abigail
authors.initials: A
authors.lastname: Zabron
authors.affiliation: Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, University of Newcastle, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Reeves
authors.affiliation: Liver Unit, Derriford Hospital, Derriford Road, Crownhill, Plymouth, Devon PL6 8DH, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Cramp
authors.affiliation: Nottingham Digestive Diseases Centre, University of Nottingham and NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ryder
authors.affiliation: Department of Gastroenterology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, United Kingdom.
authors.forename: Shaun
authors.initials: S
authors.lastname: Greer
authors.affiliation: The Foundation for Liver Research, Institute of Hepatology, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom.
authors.forename: I Jane
authors.initials: IJ
authors.lastname: Cox
authors.affiliation: The Foundation for Liver Research, Institute of Hepatology, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom.
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Liver Unit, Southampton General Hospital, Tremona Rd, Southampton, Hampshire SO16 6YD, United Kingdom.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Nash
authors.affiliation: Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, South Wharf Road, London W2 1NY, United Kingdom.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Taylor-Robinson
keywords: 1H NMR; 1H NMR, proton nuclear magnetic resonance; AFP, alpha-fetoprotein; ALT, alanine transaminase; BCLC, Barcelona Clinic Liver Cancer; BMI, body mass index; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIV, human immunodeficiency virus; INR, International Normalized Ratio; NASH, non-alcoholic steatohepatitis; PCA, principal component analysis; PLS-DA, partial least squares discriminant analysis; SEER, surveillance Epidemiology and End Results; STOCSY, statistical total correlation spectroscopy; TSP, trimethyl-silyl phosphate; US, ultrasonography; biomarkers; hepatocellular carcinoma; metabonomics