Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C

Takafumi Saito, Masahiro Sugimoto, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Kaori Igarashi, Hiroko Maki, Masaru Tomita, Yoshiyuki Ueno, Tomoyoshi Soga

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12 Citations (Scopus)


AIM: To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome analysis. METHODS: The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC (HCC-B) and hepatitis C virus-related HCC (HCC-C), respectively. RESULTS: The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 γ-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e. , concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regression model discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and γ-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94 (95%CI: 0.89-1.0, P < 0.0001). CONCLUSION: The serum levels of γ-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.

Original languageEnglish
Pages (from-to)6224-6234
Number of pages11
JournalWorld Journal of Gastroenterology
Issue number27
Publication statusPublished - 2016 Jul 21


  • Glutathione
  • Hepatocellular carcinoma
  • Metabolome
  • Oxidative stress
  • γ-glutamyl peptides

ASJC Scopus subject areas

  • Gastroenterology


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