Urinary Metabotyping of Hepatocellular Carcinoma in a UK Cohort Using Proton Nuclear Magnetic Resonance Spectroscopy

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Title: Urinary Metabotyping of Hepatocellular Carcinoma in a UK Cohort Using Proton Nuclear Magnetic Resonance Spectroscopy
Authors: Shariff, MIF
Kim, JU
Ladep, NG
Crossey, MME
Koomson, LK
Zabron, A
Reeves, H
Cramp, M
Ryder, S
Greer, S
Cox, IJ
Williams, R
Holmes, E
Nash, K
Taylor-Robinson, SD
Item Type: Journal Article
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 600MHz 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 200IUmL-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.
Issue Date: 20-Apr-2016
Date of Acceptance: 20-Mar-2016
URI: http://hdl.handle.net/10044/1/32390
DOI: http://dx.doi.org/10.1016/j.jceh.2016.03.003
ISSN: 2213-3453
Publisher: Elsevier
Start Page: 186
End Page: 194
Journal / Book Title: Journal of Clinical and Experimental Hepatology
Volume: 6
Issue: 3
Copyright Statement: © 2016 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: British Liver Trust
Trustees of the London Clinic
Funder's Grant Number: N/A
N/A
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
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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