The change of glucose and lipid metabolism in hepatocellular carcinoma and the involvement to tumor dedifferntiation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09430
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyushu University
• Principal Investigator: Kohjima Motoyuki 九州大学, 大学病院, 助教 (00650748)
• Co-Investigator(Kenkyū-buntansha): 加藤 正樹 九州大学, 医学研究院, 准教授 (60444808)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肝細胞癌 / 糖質代謝 / 脂質代謝 / Warburg effect

Outline of Final Research Achievements

The gene expressions for glycolysis and pentose phosphate pathway were increased and the expressions for TCA cycle and β-oxidation were decreased in the tissue of hepatocellular carcinoma, indicating that Warburg effect was developed in the tumor cells. The change of gene expression became predominant with the tumor progression to poorly differentiated hepatocellular carcinoma. In well differentiated hepatocellular carcinoma, the genes for fatty acid synthesis, fatty acid uptake, triglyceride synthesis were unregulated, while the genes were suppressed in poorly differentiated carcinoma. The expression change were also observed in hepatocellular carcinoma arisen in mouse model for NASH. Moreover, the metabolical change were confirmed by the alternation of metabolite in the tumor with metabolomics analysis.

Free Research Field

消化器病、肝臓病、代謝異常

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌での糖・脂質代謝関連遺伝子については、特定の遺伝子発現については検討されているが、網羅的に検討された報告は無く、悪性度の変化との関係や肝細胞癌発生母地としての背景肝組織に注目した報告はみられない。また、糖・脂質代謝改善作用を持つ薬剤による薬理学的作用や代謝産物の評価についての報告も限られている。本研究により肝細胞癌における糖・脂質代謝の変化が解明されたことで、これらを標的とした新たな治療ターゲットを開発する端緒となりうる。