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 language | English |
|---|---|
| Pages (from-to) | 986-993 |
| Number of pages | 8 |
| Journal | Hepatology Research |
| Volume | 45 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 2015 |
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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 journal › Article
}
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 -