Abstract
BackgroundAltered glycosylation associated with hepatocellular carcinoma (HCC) is well documented. However, few reports have investigated the association between dedifferentiation and glycosylation. Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation.MethodsWe analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule. Moreover, we 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.ResultsFour 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. Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones. 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.ConclusionDedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans. MGAT1 may play a role in the dedifferentiation of HCC.
Highlights
Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented
Four lectins of Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A (ConA), Galanthus nivalis agglutinin (GNA), and Calystegia sepium agglutinin (Calsepa) were significantly increased in moderately-differentiated components compared with well-differentiated components (Table 1)
All the lectins showed specificity to highmannose glycan structures and none were significantly decreased by dedifferentiation
Summary
Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented. Few reports have investigated the association between dedifferentiation and glycosylation. The aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation. Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis [1, 2]. In many kinds of cancer, aberrant glycosylation such as fucosylation and sialylation, as well as altered expression of glycosyltransferase, which modulates glycosylation, have been reported [6,7,8,9,10,11]. Fucosylated haptoglobin and fucosylated kininogen were reported to be candidates for biological markers of HCC [14, 15]
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