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 - Kinugasa, Hideaki
AU - Wada, Nozomu
AU - Takeuchi, Yasuto
AU - Kuwaki, Kenji
AU - Onishi, 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
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U2 - 10.1111/hepr.12441
DO - 10.1111/hepr.12441
M3 - Article
AN - SCOPUS:84941021960
VL - 45
SP - 986
EP - 993
JO - Hepatology Research
JF - Hepatology Research
SN - 1386-6346
IS - 9
ER -