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Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma
Journal article   Open access

Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma

Mary Ann Comunale, Lucy Rodemich-Betesh, Julie Hafner, Mengjun Wang, Pamela Norton, Adrian M Di Bisceglie, Timothy Block and Anand Mehta
PloS one, v 5(8), pp e12419-e12419
25 Aug 2010
DOI: https://doi.org/10.1371/journal.pone.0012419
PMID: 20811639
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1371/journal.pone.0012419View
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Abstract

Biomarkers - metabolism Carcinoma, Hepatocellular - diagnosis Fucose - metabolism Humans Glycosylation False Positive Reactions Case-Control Studies Disease Progression Lectins - metabolism alpha 1-Antitrypsin - chemistry Liver Neoplasms - diagnosis Protein Isoforms - metabolism Protein Isoforms - chemistry Sensitivity and Specificity Liver Cirrhosis - metabolism Liver Neoplasms - metabolism Liver Cirrhosis - pathology alpha 1-Antitrypsin - metabolism Carcinoma, Hepatocellular - metabolism Cohort Studies
We previously reported increased levels of protein-linked fucosylation with the development of liver cancer and identified many of the proteins containing the altered glycan structures. One such protein is alpha-1-antitrypsin (A1AT). To advance these studies, we performed N-linked glycan analysis on the five major isoforms of A1AT and completed a comprehensive study of the glycosylation of A1AT found in healthy controls, patients with hepatitis C- (HCV) induced liver cirrhosis, and in patients infected with HCV with a diagnosis of hepatocellular carcinoma (HCC). Patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan-containing outer arm (alpha-1,3) fucosylation. Increases in core (alpha-1,6) fucosylation were observed only on A1AT from patients with cancer. We performed a lectin fluorophore-linked immunosorbent assay using Aleuria Aurantia lectin (AAL), specific for core and outer arm fucosylation in over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC with a sensitivity of 70% and a specificity of 86%, which was greater than that observed with the current marker of HCC, alpha-fetoprotein. Glycosylation analysis of the false positives was performed; results indicated that these patients had increases in outer arm fucosylation but not in core fucosylation, suggesting that core fucosylation is cancer specific. This report details the stepwise change in the glycosylation of A1AT with the progression from liver cirrhosis to cancer and identifies core fucosylation on A1AT as an HCC specific modification.

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Gastroenterology & Hepatology
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