Mohamed I F Shariff1, Jin U Kim1, Nimzing G Ladep1, Mary M E Crossey2, Larry K Koomson1, Abigail Zabron1, Helen Reeves3, Matthew Cramp4, Stephen Ryder5, Shaun Greer6, I Jane Cox7, Roger Williams7, Elaine Holmes8, Kathryn Nash9, Simon D Taylor-Robinson1. 1. Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, South Wharf Road, London W2 1NY, United Kingdom. 2. 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. 3. Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, University of Newcastle, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom. 4. Liver Unit, Derriford Hospital, Derriford Road, Crownhill, Plymouth, Devon PL6 8DH, United Kingdom. 5. 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. 6. Department of Gastroenterology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, United Kingdom. 7. The Foundation for Liver Research, Institute of Hepatology, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom. 8. Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, United Kingdom. 9. Liver Unit, Southampton General Hospital, Tremona Rd, Southampton, Hampshire SO16 6YD, United Kingdom.
Abstract
BACKGROUND: Discriminatory metabolic profiles have been described in urinary 1H 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 MHz 1H 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. CONCLUSION: 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.
BACKGROUND: Discriminatory metabolic profiles have been described in urinary 1H 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 MHz 1H 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. CONCLUSION: 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.
Entities:
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
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