Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma

Koji Miyahara, Kazuhiro Nouso, Chihiro Dohi, Yuki Morimoto, Hideaki Kunugasa, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Ohnishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Maho Amano, Shin Ichiro Nishimura, Kazuhide Yamamoto

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Aim: Most of the modification of N-glycosylation reported in cancers including hepatocellular carcinoma (HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N-glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application. Methods: We analyzed sera from 105 patients with chronic hepatitis/liver cirrhosis (CH/LC) and age-/sex-matched healthy volunteers (HLT), as well as from 114 patients with HCC. Serum N-glycan profiles were measured comprehensively by a new, quantitative, high-throughput method and compared with clinical parameters. Results: The total amount of N-glycan expression was significantly higher in patients with CH/LC than in HLT; however, no differences were observed between CH/LC and HCC patients. In HCC patients, multi-antennary glycans with fucose residues, particularly m/z 3195, were increased compared with CH/LC patients. The expression of m/z 3195 was high, especially in patients with a high number of intrahepatic lesions (>3), large tumor size (>3cm), macroscopic vascular invasion or metastasis. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) showed a higher area under the receiver-operator curve of 0.810 than any other single glycan to distinguish HCC from CH/LC. Conclusion: We demonstrate the full spectrum of the alterations of serum N-glycans comprehensively in patients with liver disease, and elucidate the possible use of glycans as novel biomarkers of liver disease progression.

Original languageEnglish
Pages (from-to)986-993
Number of pages8
JournalHepatology Research
Volume45
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

Fingerprint

Chronic Hepatitis
Polysaccharides
Hepatocellular Carcinoma
Liver Cirrhosis
Serum
Liver Diseases
Healthy Volunteers
Fucose
Glycosylation
Blood Vessels
Disease Progression
Neoplasms
Biomarkers
Neoplasm Metastasis

Keywords

  • Biomarker
  • Diagnosis
  • Hepatocellular carcinoma
  • Liver disease
  • N-glycan

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

Cite this

Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma. / Miyahara, Koji; Nouso, Kazuhiro; Dohi, Chihiro; Morimoto, Yuki; Kunugasa, Hideaki; Wada, Nozomu; Takeuchi, Yasuto; Kuwaki, Kenji; Ohnishi, Hideki; Ikeda, Fusao; Miyake, Yasuhiro; Nakamura, Shinichiro; Shiraha, Hidenori; Takaki, Akinobu; Amano, Maho; Nishimura, Shin Ichiro; Yamamoto, Kazuhide.

In: Hepatology Research, Vol. 45, No. 9, 01.09.2015, p. 986-993.

Research output: Contribution to journalArticle

Miyahara, K, Nouso, K, Dohi, C, Morimoto, Y, Kunugasa, H, Wada, N, Takeuchi, Y, Kuwaki, K, Ohnishi, H, Ikeda, F, Miyake, Y, Nakamura, S, Shiraha, H, Takaki, A, Amano, M, Nishimura, SI & Yamamoto, K 2015, 'Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma', Hepatology Research, vol. 45, no. 9, pp. 986-993. https://doi.org/10.1111/hepr.12441
Miyahara, Koji ; Nouso, Kazuhiro ; Dohi, Chihiro ; Morimoto, Yuki ; Kunugasa, Hideaki ; Wada, Nozomu ; Takeuchi, Yasuto ; Kuwaki, Kenji ; Ohnishi, Hideki ; Ikeda, Fusao ; Miyake, Yasuhiro ; Nakamura, Shinichiro ; Shiraha, Hidenori ; Takaki, Akinobu ; Amano, Maho ; Nishimura, Shin Ichiro ; Yamamoto, Kazuhide. / Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma. In: Hepatology Research. 2015 ; Vol. 45, No. 9. pp. 986-993.
@article{c1c7dae5300247b39dacd6933ca84f8c,
title = "Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma",
abstract = "Aim: Most of the modification of N-glycosylation reported in cancers including hepatocellular carcinoma (HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N-glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application. Methods: We analyzed sera from 105 patients with chronic hepatitis/liver cirrhosis (CH/LC) and age-/sex-matched healthy volunteers (HLT), as well as from 114 patients with HCC. Serum N-glycan profiles were measured comprehensively by a new, quantitative, high-throughput method and compared with clinical parameters. Results: The total amount of N-glycan expression was significantly higher in patients with CH/LC than in HLT; however, no differences were observed between CH/LC and HCC patients. In HCC patients, multi-antennary glycans with fucose residues, particularly m/z 3195, were increased compared with CH/LC patients. The expression of m/z 3195 was high, especially in patients with a high number of intrahepatic lesions (>3), large tumor size (>3cm), macroscopic vascular invasion or metastasis. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) showed a higher area under the receiver-operator curve of 0.810 than any other single glycan to distinguish HCC from CH/LC. Conclusion: We demonstrate the full spectrum of the alterations of serum N-glycans comprehensively in patients with liver disease, and elucidate the possible use of glycans as novel biomarkers of liver disease progression.",
keywords = "Biomarker, Diagnosis, Hepatocellular carcinoma, Liver disease, N-glycan",
author = "Koji Miyahara and Kazuhiro Nouso and Chihiro Dohi and Yuki Morimoto and Hideaki Kunugasa and Nozomu Wada and Yasuto Takeuchi and Kenji Kuwaki and Hideki Ohnishi and Fusao Ikeda and Yasuhiro Miyake and Shinichiro Nakamura and Hidenori Shiraha and Akinobu Takaki and Maho Amano and Nishimura, {Shin Ichiro} and Kazuhide Yamamoto",
year = "2015",
month = "9",
day = "1",
doi = "10.1111/hepr.12441",
language = "English",
volume = "45",
pages = "986--993",
journal = "Hepatology Research",
issn = "1386-6346",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma

AU - Miyahara, Koji

AU - Nouso, Kazuhiro

AU - Dohi, Chihiro

AU - Morimoto, Yuki

AU - Kunugasa, Hideaki

AU - Wada, Nozomu

AU - Takeuchi, Yasuto

AU - Kuwaki, Kenji

AU - Ohnishi, Hideki

AU - Ikeda, Fusao

AU - Miyake, Yasuhiro

AU - Nakamura, Shinichiro

AU - Shiraha, Hidenori

AU - Takaki, Akinobu

AU - Amano, Maho

AU - Nishimura, Shin Ichiro

AU - Yamamoto, Kazuhide

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Aim: Most of the modification of N-glycosylation reported in cancers including hepatocellular carcinoma (HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N-glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application. Methods: We analyzed sera from 105 patients with chronic hepatitis/liver cirrhosis (CH/LC) and age-/sex-matched healthy volunteers (HLT), as well as from 114 patients with HCC. Serum N-glycan profiles were measured comprehensively by a new, quantitative, high-throughput method and compared with clinical parameters. Results: The total amount of N-glycan expression was significantly higher in patients with CH/LC than in HLT; however, no differences were observed between CH/LC and HCC patients. In HCC patients, multi-antennary glycans with fucose residues, particularly m/z 3195, were increased compared with CH/LC patients. The expression of m/z 3195 was high, especially in patients with a high number of intrahepatic lesions (>3), large tumor size (>3cm), macroscopic vascular invasion or metastasis. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) showed a higher area under the receiver-operator curve of 0.810 than any other single glycan to distinguish HCC from CH/LC. Conclusion: We demonstrate the full spectrum of the alterations of serum N-glycans comprehensively in patients with liver disease, and elucidate the possible use of glycans as novel biomarkers of liver disease progression.

AB - Aim: Most of the modification of N-glycosylation reported in cancers including hepatocellular carcinoma (HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N-glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application. Methods: We analyzed sera from 105 patients with chronic hepatitis/liver cirrhosis (CH/LC) and age-/sex-matched healthy volunteers (HLT), as well as from 114 patients with HCC. Serum N-glycan profiles were measured comprehensively by a new, quantitative, high-throughput method and compared with clinical parameters. Results: The total amount of N-glycan expression was significantly higher in patients with CH/LC than in HLT; however, no differences were observed between CH/LC and HCC patients. In HCC patients, multi-antennary glycans with fucose residues, particularly m/z 3195, were increased compared with CH/LC patients. The expression of m/z 3195 was high, especially in patients with a high number of intrahepatic lesions (>3), large tumor size (>3cm), macroscopic vascular invasion or metastasis. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) showed a higher area under the receiver-operator curve of 0.810 than any other single glycan to distinguish HCC from CH/LC. Conclusion: We demonstrate the full spectrum of the alterations of serum N-glycans comprehensively in patients with liver disease, and elucidate the possible use of glycans as novel biomarkers of liver disease progression.

KW - Biomarker

KW - Diagnosis

KW - Hepatocellular carcinoma

KW - Liver disease

KW - N-glycan

UR - http://www.scopus.com/inward/record.url?scp=84941021960&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941021960&partnerID=8YFLogxK

U2 - 10.1111/hepr.12441

DO - 10.1111/hepr.12441

M3 - Article

VL - 45

SP - 986

EP - 993

JO - Hepatology Research

JF - Hepatology Research

SN - 1386-6346

IS - 9

ER -