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

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.