Altered Glycosylation Associated with Dedifferentiation of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Liver cancer is the sixth most common type of cancer worldwide, and the fourth most common cause of cancer death. HCC accounts for most primary liver cancers.

Glycosylation is involved in many essential biological processes such as cell differentiation, proliferation, and adhesion; immune response; and receptor activation. However, aberrant glycosylation results in many dysfunctions and diseases. Lectin microarray is a method capable of analyzing glycan profiles comprehensively and sensitively with 45 lectins utilizing lectin specificity to detect specific structures of glycans.

Gastroenterologists at the Oita University Faculty of Medicine (Oita, Japan) analyzed resected 50 HCC specimens using lectin microarray to comprehensively and sensitively analyze glycan profiles. The samples were prepared for laser microdissection by fixing in formalin, embedding in paraffin, then sectioning at a thickness of 5 μm. Lectin microarray was performed and performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans. Fluorescent images were obtained with the GlycoStation Reader 1200 (GlycoTechnica Ltd, Yokohama, Japan) using the evanescent-wave excitation method.

The scientists reported that four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans. All the lectins showed specificity to high-mannose glycan structures and none were significantly decreased by dedifferentiation. Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components. Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.

The authors concluded that dedifferentiation of well-differentiated HCC is associated with increased high-mannose glycans. Furthermore, MGAT1 may play a role in HCC dedifferentiation. The study was published on March 6, 2020 in the journal BMC Cancer.

Related Links:
Oita University Faculty of Medicine
GlycoTechnica Ltd