title: Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okumoto
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Haga
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsumi
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Nishina
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Sonoko
authors.initials: S
authors.lastname: Sato
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Maki
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053801:Capillary Electrochromatography; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000378:metabolism*; D005260:Female; D005978:Glutathione; D019694:Hepatitis B, Chronic / Q000150:complications / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D008875:Middle Aged; D018384:Oxidative Stress; D012372:ROC Curve
chemical_list: D005978:Glutathione
keywords: Glutathione; Hepatocellular carcinoma; Metabolome; Oxidative stress; γ-glutamyl peptides