Serum Mac-2 binding protein levels as a novel diagnostic biomarker for prediction of disease severity and nonalcoholic steatohepatitis

Proteomics Clin Appl. 2013 Oct;7(9-10):648-56. doi: 10.1002/prca.201200137. Epub 2013 Sep 17.

Abstract

Purpose: Mac-2 binding protein (Mac-2 bp) is one of the major fucosylated glycoproteins, which we identified with glycol-proteomic analyses. We previously reported that fucosylated glycoproteins are secreted into bile, but scarcely secreted into sera in normal liver and hypothesized that the fucosylation-based sorting machinery would be disrupted in ballooning hepatocytes due to the loss of cellular polarity. In the present study, we investigated the availability of Mac-2 bp for differential diagnosis of nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD) as a biomarker.

Experimental design: Serum Mac-2 bp levels were determined with our developed ELISA kit. Our cohort of 127 patients with NAFLD had liver biopsy to make a histological diagnosis of NASH and simple fatty liver.

Results: Mac-2 bp levels were significantly elevated in NASH patients compared with non-NASH (simple steatosis) patients (2.132 ± 1.237 vs. 1.103 ± 0.500 μg/mL, p < 0.01). The area under the receiver-operating characteristic curve for predicting NASH by Mac-2 bp was 0.816. Moreover, multivariate logistic regression analyses showed Mac-2 bp levels could predict the fibrosis stage and the presence of ballooning hepatocytes in NAFLD patients.

Conclusions and clinical relevance: These results support the potential usefulness of measuring Mac-2 bp levels in clinical practice as a biomarker for NASH.

Keywords: Ballooning hepatocyte; Liver fibrosis; Mac-2bp/90K; N-glycan; NASH/NAFLD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / blood*
  • Antigens, Neoplasm / metabolism
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Line
  • Female
  • Fucose / metabolism
  • Humans
  • Male
  • Membrane Glycoproteins / blood*
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Prognosis

Substances

  • Antigens, Neoplasm
  • Biomarkers
  • Membrane Glycoproteins
  • TAA90K protein, human
  • Fucose