Glycan profiling relation to dedifferentiation of hepatocellular carcinoma with lectin microarray

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16572
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Oita University
• Principal Investigator: Takayama Hiroomi 大分大学, 医学部, 客員研究員 (50733614)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肝細胞癌 / レクチン / 糖鎖プロファイリング / 脱分化 / 糖転移酵素 / 高マンノース型糖鎖 / MGAT1

Outline of Final Research Achievements

We investigated glycosylation associated with the dedifferentiation of HCC within the same nodule, and glycosyltransferase related to the glycosylation.
We analyzed fifty HCC specimens using lectin microarray. Four lectins of NPA, Con A, GNA, and Calsepa were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans. Immunohistochemical staining of MGAT1, which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans, showed significantly decreased expression in moderately-differentiated components. Low MGAT1 expression was associated with intrahepatic metastasis and had tendency for poor prognosis. Dedifferentiation of HCC is associated with an increase in high-mannose glycans, and MGAT1 may play a role in the dedifferentiation of HCC.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では、同一腫瘍内で分化度の異なる成分を有する肝細胞癌について、発現する糖鎖変化を解析することで、脱分化に伴う糖鎖変化を明らかにした。高マンノース型糖鎖が脱分化に伴い増加していると考えられ、肝内転移や予後にも影響していることが示唆された。その糖鎖変化や関連する糖転移酵素の意義や機能解明までには至らなかったが、今後それらを明らかにすることで、脱分化メカニズムの解明や、脱分化制御による悪性化の制御、肝細胞癌の治療薬開発にも繋がると考えられた。