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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6224-6234
Number of pages11
JournalWorld Journal of Gastroenterology
Volume22
Issue number27
DOIs
Publication statusPublished - 2016 Jul 21

Fingerprint

Metabolome
Hepatitis C
Hepatitis B
Hepatocellular Carcinoma
Serum
Glycine
glutamyl-glutamic acid
Glutathione
Logistic Models
Viruses
Peptides
Capillary Electrophoresis

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C. / Saito, Takafumi; Sugimoto, Masahiro; Okumoto, Kazuo; Haga, Hiroaki; Katsumi, Tomohiro; Mizuno, Kei; Nishina, Taketo; Sato, Sonoko; Igarashi, Kaori; Maki, Hiroko; Tomita, Masaru; Ueno, Yoshiyuki; Soga, Tomoyoshi.

In: World Journal of Gastroenterology, Vol. 22, No. 27, 21.07.2016, p. 6224-6234.

Research output: Contribution to journalArticle

Saito, T, Sugimoto, M, Okumoto, K, Haga, H, Katsumi, T, Mizuno, K, Nishina, T, Sato, S, Igarashi, K, Maki, H, Tomita, M, Ueno, Y & Soga, T 2016, 'Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C', World Journal of Gastroenterology, vol. 22, no. 27, pp. 6224-6234. https://doi.org/10.3748/wjg.v22.i27.6224
Saito, Takafumi ; Sugimoto, Masahiro ; Okumoto, Kazuo ; Haga, Hiroaki ; Katsumi, Tomohiro ; Mizuno, Kei ; Nishina, Taketo ; Sato, Sonoko ; Igarashi, Kaori ; Maki, Hiroko ; Tomita, Masaru ; Ueno, Yoshiyuki ; Soga, Tomoyoshi. / Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C. In: World Journal of Gastroenterology. 2016 ; Vol. 22, No. 27. pp. 6224-6234.
@article{a85bd9f1a57545b8b1afeeb3cae637aa,
title = "Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C",
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 = "Glutathione, Hepatocellular carcinoma, Metabolome, Oxidative stress, γ-glutamyl peptides",
author = "Takafumi Saito and Masahiro Sugimoto and Kazuo Okumoto and Hiroaki Haga and Tomohiro Katsumi and Kei Mizuno and Taketo Nishina and Sonoko Sato and Kaori Igarashi and Hiroko Maki and Masaru Tomita and Yoshiyuki Ueno and Tomoyoshi Soga",
year = "2016",
month = "7",
day = "21",
doi = "10.3748/wjg.v22.i27.6224",
language = "English",
volume = "22",
pages = "6224--6234",
journal = "World Journal of Gastroenterology",
issn = "1007-9327",
publisher = "WJG Press",
number = "27",

}

TY - JOUR

T1 - Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C

AU - Saito, Takafumi

AU - Sugimoto, Masahiro

AU - Okumoto, Kazuo

AU - Haga, Hiroaki

AU - Katsumi, Tomohiro

AU - Mizuno, Kei

AU - Nishina, Taketo

AU - Sato, Sonoko

AU - Igarashi, Kaori

AU - Maki, Hiroko

AU - Tomita, Masaru

AU - Ueno, Yoshiyuki

AU - Soga, Tomoyoshi

PY - 2016/7/21

Y1 - 2016/7/21

N2 - 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.

AB - 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.

KW - Glutathione

KW - Hepatocellular carcinoma

KW - Metabolome

KW - Oxidative stress

KW - γ-glutamyl peptides

UR - http://www.scopus.com/inward/record.url?scp=84978524896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978524896&partnerID=8YFLogxK

U2 - 10.3748/wjg.v22.i27.6224

DO - 10.3748/wjg.v22.i27.6224

M3 - Article

C2 - 27468212

AN - SCOPUS:84978524896

VL - 22

SP - 6224

EP - 6234

JO - World Journal of Gastroenterology

JF - World Journal of Gastroenterology

SN - 1007-9327

IS - 27

ER -