Mass-selected site-specific core-fucosylation of ceruloplasmin in alcohol-related hepatocellular carcinoma

Haidi Yin, Zhenxin Lin, Song Nie, Jing Wu, Zhijing Tan, Jianhui Zhu, Jianliang Dai, Ziding Feng, Jorge Marrero, David M. Lubman

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A mass spectrometry-based methodology has been developed to study changes in core-fucosylation of serum ceruloplasmin that are site-specific between cirrhosis and hepatocellular carcinoma (HCC). The serum samples studied for these changes were from patients affected by cirrhosis or HCC with different etiologies, including alcohol, hepatitis B virus, or hepatitis C virus. The methods involved trypsin digestion of ceruloplasmin into peptides followed by Endo F3 digestion, which removed most of the glycan structure while retaining the innermost N-acetylglucosamine (GlcNAc) and/or core-fucose bound to the peptide. This procedure simplified the structures for further analysis by mass spectrometry, where four core-fucosylated sites (sites 138, 358, 397, and 762) were detected in ceruloplasmin. The core-fucosylation ratio of three of these sites increased significantly in alcohol-related HCC samples (sample size = 24) compared to that in alcohol-related cirrhosis samples (sample size = 18), with the highest AUC value of 0.838 at site 138. When combining the core-fucosylation ratio of site 138 in ceruloplasmin and the alpha-fetoprotein (AFP) value, the AUC value increased to 0.954 (ORsite138 = 12.26, p = 0.017; OR AFP = 3.64, p = 0.022), which was markedly improved compared to that of AFP (AUC = 0.867) (LR test p = 0.0002) alone. However, in HBV- or HCV-related liver diseases, no significant site-specific change in core-fucosylation of ceruloplasmin was observed between HCC and cirrhosis.

Original languageEnglish (US)
Pages (from-to)2887-2896
Number of pages10
JournalJournal of Proteome Research
Volume13
Issue number6
DOIs
StatePublished - Jun 6 2014

Fingerprint

Ceruloplasmin
Hepatocellular Carcinoma
Alcohols
alpha-Fetoproteins
Fibrosis
Area Under Curve
Viruses
Sample Size
Mass spectrometry
Digestion
Mass Spectrometry
Peptides
Fucose
Acetylglucosamine
Serum
Hepatitis B virus
Hepacivirus
Liver
Trypsin
Polysaccharides

Keywords

  • ceruloplasmin
  • Core-fucosylation
  • hepatocellular carcinoma
  • site specific

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)
  • Medicine(all)

Cite this

Mass-selected site-specific core-fucosylation of ceruloplasmin in alcohol-related hepatocellular carcinoma. / Yin, Haidi; Lin, Zhenxin; Nie, Song; Wu, Jing; Tan, Zhijing; Zhu, Jianhui; Dai, Jianliang; Feng, Ziding; Marrero, Jorge; Lubman, David M.

In: Journal of Proteome Research, Vol. 13, No. 6, 06.06.2014, p. 2887-2896.

Research output: Contribution to journalArticle

Yin, Haidi ; Lin, Zhenxin ; Nie, Song ; Wu, Jing ; Tan, Zhijing ; Zhu, Jianhui ; Dai, Jianliang ; Feng, Ziding ; Marrero, Jorge ; Lubman, David M. / Mass-selected site-specific core-fucosylation of ceruloplasmin in alcohol-related hepatocellular carcinoma. In: Journal of Proteome Research. 2014 ; Vol. 13, No. 6. pp. 2887-2896.
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AU - Zhu, Jianhui

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AU - Feng, Ziding

AU - Marrero, Jorge

AU - Lubman, David M.

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N2 - A mass spectrometry-based methodology has been developed to study changes in core-fucosylation of serum ceruloplasmin that are site-specific between cirrhosis and hepatocellular carcinoma (HCC). The serum samples studied for these changes were from patients affected by cirrhosis or HCC with different etiologies, including alcohol, hepatitis B virus, or hepatitis C virus. The methods involved trypsin digestion of ceruloplasmin into peptides followed by Endo F3 digestion, which removed most of the glycan structure while retaining the innermost N-acetylglucosamine (GlcNAc) and/or core-fucose bound to the peptide. This procedure simplified the structures for further analysis by mass spectrometry, where four core-fucosylated sites (sites 138, 358, 397, and 762) were detected in ceruloplasmin. The core-fucosylation ratio of three of these sites increased significantly in alcohol-related HCC samples (sample size = 24) compared to that in alcohol-related cirrhosis samples (sample size = 18), with the highest AUC value of 0.838 at site 138. When combining the core-fucosylation ratio of site 138 in ceruloplasmin and the alpha-fetoprotein (AFP) value, the AUC value increased to 0.954 (ORsite138 = 12.26, p = 0.017; OR AFP = 3.64, p = 0.022), which was markedly improved compared to that of AFP (AUC = 0.867) (LR test p = 0.0002) alone. However, in HBV- or HCV-related liver diseases, no significant site-specific change in core-fucosylation of ceruloplasmin was observed between HCC and cirrhosis.

AB - A mass spectrometry-based methodology has been developed to study changes in core-fucosylation of serum ceruloplasmin that are site-specific between cirrhosis and hepatocellular carcinoma (HCC). The serum samples studied for these changes were from patients affected by cirrhosis or HCC with different etiologies, including alcohol, hepatitis B virus, or hepatitis C virus. The methods involved trypsin digestion of ceruloplasmin into peptides followed by Endo F3 digestion, which removed most of the glycan structure while retaining the innermost N-acetylglucosamine (GlcNAc) and/or core-fucose bound to the peptide. This procedure simplified the structures for further analysis by mass spectrometry, where four core-fucosylated sites (sites 138, 358, 397, and 762) were detected in ceruloplasmin. The core-fucosylation ratio of three of these sites increased significantly in alcohol-related HCC samples (sample size = 24) compared to that in alcohol-related cirrhosis samples (sample size = 18), with the highest AUC value of 0.838 at site 138. When combining the core-fucosylation ratio of site 138 in ceruloplasmin and the alpha-fetoprotein (AFP) value, the AUC value increased to 0.954 (ORsite138 = 12.26, p = 0.017; OR AFP = 3.64, p = 0.022), which was markedly improved compared to that of AFP (AUC = 0.867) (LR test p = 0.0002) alone. However, in HBV- or HCV-related liver diseases, no significant site-specific change in core-fucosylation of ceruloplasmin was observed between HCC and cirrhosis.

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