Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan.
Global Oita Medical Advanced Research Center for Health, Oita University, Oita, Japan.
BMC Cancer. 2020 Mar 6;20(1):192. doi: 10.1186/s12885-020-6699-5.
Altered 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.
We 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.
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. 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.
Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans. MGAT1 may play a role in the dedifferentiation of HCC.
与肝细胞癌（HCC）相关的糖基化改变已有大量文献记载。然而，很少有报道研究去分化与糖基化之间的关系。因此，本研究旨在分析同一结节内 HCC 去分化相关的糖基化，并探讨与糖基化相关的糖基转移酶。
我们使用凝集素微阵列分析了 50 例切除的 HCC 标本，以全面、敏感地分析聚糖谱，并确定同一结节内高分化和中分化成分之间糖基化的变化。此外，我们还对甘露糖（α-1,3-）-糖蛋白β-1,2-N-乙酰氨基葡萄糖基转移酶（MGAT1）进行了免疫组织化学染色，MGAT1 是一种将高甘露糖糖基转化为复杂型或杂合型 N-聚糖的必需糖基转移酶。
水仙花凝集素（NPA）、刀豆凝集素、雪花莲凝集素和长春花凝集素这 4 种凝集素在中分化 HCC 成分中的表达明显高于高分化成分，所有凝集素均显示出与高甘露糖聚糖的结合特异性。因此，这些结构在中分化成分中比在高分化成分中更广泛地表达。免疫组织化学染色显示，中分化成分中的 NPA 表达增加，MGAT1 表达减少。肿瘤中分化成分中 MGAT1 表达较低与肝内转移有关，且预后较差。
高分化 HCC 的去分化与高甘露糖聚糖的增加有关。MGAT1 可能在 HCC 的去分化中起作用。
