Novel changes in glycosylation of serum Apo-J in patients with hepatocellular carcinoma

Mary Ann Comunale, Mengjun Wang, Lucy Rodemich-Betesh, Julie Hafner, Anne Lamontagne, Andrew Klein, Jorge Marrero, Adrian M. Di Bisceglie, Robert Gish, Timothy Block, Anand Mehta

Research output: Contribution to journalArticle

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Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the occurrence of HCC has more than doubled in the United States in the past decade. Early detection is considered key to reducing the mortality of HCC. Methods: Using two-dimensional gel electrophoresis and high-performance liquid chromatography we have analyzed the glycosylation of Apo-J from healthy controls, patients with liver cirrhosis, or those with HCC. Results: Apo-J in the serum from patients with HCC had decreased levels of (β-1,4) triantennary N-linked glycan compared with the healthy controls or patients with liver cirrhosis. We analyzed this change in an independent cohort of 76 patients with HCC, 32 with cirrhosis, and 43 infected with hepatitis C virus using the Datura stramonium lectin (DSL), which binds to (β-1,4) triantennary N-linked glycan. The level of DSL-reactive Apo-J allowed us to differentiate HCC from cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.852. When Apo-J was combined with other serum biomarkers such as α-fetoprotein (AFP) and fucosylated kininogen by using a multivariate logistic regression model, the AUROC increased to 0.944, a value much greater than that observed with AFP alone (AUROC of 0.765). Conclusions: The glycosylation of Apo-J is a useful marker when used alone or in combination with outer makers for the early detection of HCC. Impact: The potential use of a combination of AFP, DSL-reactive Apo-J, and fucosylated kininogen as a biomarker of HCC would have great value in the management of patients with liver disease.

Original languageEnglish (US)
Pages (from-to)1222-1229
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume20
Issue number6
DOIs
StatePublished - Jun 2011

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Glycosylation
Hepatocellular Carcinoma
Serum
Fetal Proteins
ROC Curve
Kininogens
Liver Cirrhosis
Polysaccharides
Fibrosis
Biomarkers
Logistic Models
Electrophoresis, Gel, Two-Dimensional
Hepacivirus
Liver Diseases
High Pressure Liquid Chromatography
Mortality

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Comunale, M. A., Wang, M., Rodemich-Betesh, L., Hafner, J., Lamontagne, A., Klein, A., ... Mehta, A. (2011). Novel changes in glycosylation of serum Apo-J in patients with hepatocellular carcinoma. Cancer Epidemiology Biomarkers and Prevention, 20(6), 1222-1229. https://doi.org/10.1158/1055-9965.EPI-10-1047

Novel changes in glycosylation of serum Apo-J in patients with hepatocellular carcinoma. / Comunale, Mary Ann; Wang, Mengjun; Rodemich-Betesh, Lucy; Hafner, Julie; Lamontagne, Anne; Klein, Andrew; Marrero, Jorge; Di Bisceglie, Adrian M.; Gish, Robert; Block, Timothy; Mehta, Anand.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 20, No. 6, 06.2011, p. 1222-1229.

Research output: Contribution to journalArticle

Comunale, MA, Wang, M, Rodemich-Betesh, L, Hafner, J, Lamontagne, A, Klein, A, Marrero, J, Di Bisceglie, AM, Gish, R, Block, T & Mehta, A 2011, 'Novel changes in glycosylation of serum Apo-J in patients with hepatocellular carcinoma', Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 6, pp. 1222-1229. https://doi.org/10.1158/1055-9965.EPI-10-1047
Comunale, Mary Ann ; Wang, Mengjun ; Rodemich-Betesh, Lucy ; Hafner, Julie ; Lamontagne, Anne ; Klein, Andrew ; Marrero, Jorge ; Di Bisceglie, Adrian M. ; Gish, Robert ; Block, Timothy ; Mehta, Anand. / Novel changes in glycosylation of serum Apo-J in patients with hepatocellular carcinoma. In: Cancer Epidemiology Biomarkers and Prevention. 2011 ; Vol. 20, No. 6. pp. 1222-1229.
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T1 - Novel changes in glycosylation of serum Apo-J in patients with hepatocellular carcinoma

AU - Comunale, Mary Ann

AU - Wang, Mengjun

AU - Rodemich-Betesh, Lucy

AU - Hafner, Julie

AU - Lamontagne, Anne

AU - Klein, Andrew

AU - Marrero, Jorge

AU - Di Bisceglie, Adrian M.

AU - Gish, Robert

AU - Block, Timothy

AU - Mehta, Anand

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N2 - Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the occurrence of HCC has more than doubled in the United States in the past decade. Early detection is considered key to reducing the mortality of HCC. Methods: Using two-dimensional gel electrophoresis and high-performance liquid chromatography we have analyzed the glycosylation of Apo-J from healthy controls, patients with liver cirrhosis, or those with HCC. Results: Apo-J in the serum from patients with HCC had decreased levels of (β-1,4) triantennary N-linked glycan compared with the healthy controls or patients with liver cirrhosis. We analyzed this change in an independent cohort of 76 patients with HCC, 32 with cirrhosis, and 43 infected with hepatitis C virus using the Datura stramonium lectin (DSL), which binds to (β-1,4) triantennary N-linked glycan. The level of DSL-reactive Apo-J allowed us to differentiate HCC from cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.852. When Apo-J was combined with other serum biomarkers such as α-fetoprotein (AFP) and fucosylated kininogen by using a multivariate logistic regression model, the AUROC increased to 0.944, a value much greater than that observed with AFP alone (AUROC of 0.765). Conclusions: The glycosylation of Apo-J is a useful marker when used alone or in combination with outer makers for the early detection of HCC. Impact: The potential use of a combination of AFP, DSL-reactive Apo-J, and fucosylated kininogen as a biomarker of HCC would have great value in the management of patients with liver disease.

AB - Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the occurrence of HCC has more than doubled in the United States in the past decade. Early detection is considered key to reducing the mortality of HCC. Methods: Using two-dimensional gel electrophoresis and high-performance liquid chromatography we have analyzed the glycosylation of Apo-J from healthy controls, patients with liver cirrhosis, or those with HCC. Results: Apo-J in the serum from patients with HCC had decreased levels of (β-1,4) triantennary N-linked glycan compared with the healthy controls or patients with liver cirrhosis. We analyzed this change in an independent cohort of 76 patients with HCC, 32 with cirrhosis, and 43 infected with hepatitis C virus using the Datura stramonium lectin (DSL), which binds to (β-1,4) triantennary N-linked glycan. The level of DSL-reactive Apo-J allowed us to differentiate HCC from cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.852. When Apo-J was combined with other serum biomarkers such as α-fetoprotein (AFP) and fucosylated kininogen by using a multivariate logistic regression model, the AUROC increased to 0.944, a value much greater than that observed with AFP alone (AUROC of 0.765). Conclusions: The glycosylation of Apo-J is a useful marker when used alone or in combination with outer makers for the early detection of HCC. Impact: The potential use of a combination of AFP, DSL-reactive Apo-J, and fucosylated kininogen as a biomarker of HCC would have great value in the management of patients with liver disease.

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