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

doi:10.3748/wjg.v22.i27.6224

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Jul 21, 2016; 22(27): 6224-6234
Published online Jul 21, 2016. doi: 10.3748/wjg.v22.i27.6224

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

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

Masahiro Sugimoto, Kaori Igarashi, Hiroko Maki, Masaru Tomita, Tomoyoshi Soga, Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan

Author contributions: Saito T and Sugimoto M analyzed the data and equally contributed as the lead author of this manuscript; Soga T conducted the study as the principal investigator; Tomita M and Ueno Y participated in the study coordination as the chief of laboratory, Keio and Yamagata University, respectively; Okumoto K, Haga H, Katsumi T, Mizuno K and Nishina T provided medical care and collected the sample; Sato S, Igarashi K and Maki H performed the metabolome assay; all authors read and approved the manuscript.

Supported by the Japan Agency for Medical Research and Development; and Yamagata Prefectural Government and City of Tsuruoka.

Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Yamagata University School of Medicine and Keio University Institute for Advanced Biosciences.

Conflict-of-interest statement: The authors have no conflict of interest.

Data sharing statement: No additional data are available.

Correspondence to: Takafumi Saito, MD, Associate Professor of Gastroenterology, Department of Gastroenterology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, Yamagata 990-9585, Japan. tasaitoh@med.id.yamagata-u.ac.jp

Telephone: +81-23-6285309 Fax: +81-23-6285311

Received: April 1, 2016
Peer-review started: April 7, 2016
First decision: May 12, 2016
Revised: May 25, 2016
Accepted: June 15, 2016
Article in press: June 15, 2016
Published online: July 21, 2016
Processing time: 105 Days and 5 Hours

Abstract

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.

Keywords: Metabolome; Hepatocellular carcinoma; γ-glutamyl peptides; Glutathione; Oxidative stress

Core tip: Serum metabolome analysis was applied to the patients of hepatocellular carcinoma (HCC) infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) to clarify the characteristics of their metabolite profiles. This study demonstrated that the serum concentrations of γ-glutamyl peptides and their concentration patterns contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between the HCC patients infected with HBV and HCV may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.