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

Abstract

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. 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). 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. 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.