Analysis of serum haptoglobin fucosylation in hepatocellular carcinoma and liver cirrhosis of different etiologies

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

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

We have developed herein a quantitative mass spectrometry-based approach to analyze the etiology-related alterations in fucosylation degree of serum haptoglobin in patients with liver cirrhosis and hepatocellular carcinoma (HCC). The three most common etiologies, including infection with hepatitis B virus (HBV), infection with hepatitis C virus (HCV), and heavy alcohol consumption (ALC), were investigated. Only 10 μL of serum was used in this assay in which haptoglobin was immunoprecipitated using a monoclonal antibody. The N-glycans of haptoglobin were released with PNGase F, desialylated, and permethylated prior to MALDI-QIT-TOF MS analysis. In total, N-glycan profiles derived from 104 individual patient samples were quantified (14 healthy controls, 40 cirrhosis, and 50 HCCs). A unique pattern of bifucosylated tetra-antennary glycan, with both core and antennary fucosylation, was identified in HCC patients. Quantitative analysis indicated that the increased fucosylation degree was highly associated with HBV- and ALC-related HCC patients compared to that of the corresponding cirrhosis patients. Notably, the bifucosylation degree was distinctly increased in HCC patients versus that in cirrhosis of all etiologies. The elevated bifucosylation degree of haptoglobin can discriminate early stage HCC patients from cirrhosis in each etiologic category, which may be used to provide a potential marker for early detection and to predict HCC in patients with cirrhosis.

Original languageEnglish (US)
Pages (from-to)2986-2997
Number of pages12
JournalJournal of Proteome Research
Volume13
Issue number6
DOIs
StatePublished - Jun 6 2014

Fingerprint

Haptoglobins
Liver Cirrhosis
Liver
Hepatocellular Carcinoma
Viruses
Polysaccharides
Serum
Fibrosis
Alcohols
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
Hepatitis B virus
Alcohol Drinking
Mass spectrometry
Assays
Monoclonal Antibodies
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Virus Diseases
Chemical analysis
Hepacivirus
Mass Spectrometry

Keywords

  • biomarker
  • fucosylation
  • haptoglobin
  • Hepatocellular carcinoma
  • liver cirrhosis
  • MALDI

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Analysis of serum haptoglobin fucosylation in hepatocellular carcinoma and liver cirrhosis of different etiologies. / Zhu, Jianhui; Lin, Zhenxin; Wu, Jing; Yin, Haidi; Dai, Jianliang; Feng, Ziding; Marrero, Jorge; Lubman, David M.

In: Journal of Proteome Research, Vol. 13, No. 6, 06.06.2014, p. 2986-2997.

Research output: Contribution to journalArticle

Zhu, Jianhui ; Lin, Zhenxin ; Wu, Jing ; Yin, Haidi ; Dai, Jianliang ; Feng, Ziding ; Marrero, Jorge ; Lubman, David M. / Analysis of serum haptoglobin fucosylation in hepatocellular carcinoma and liver cirrhosis of different etiologies. In: Journal of Proteome Research. 2014 ; Vol. 13, No. 6. pp. 2986-2997.
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