The role of ferroptosis in hepatocellular carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyushu University
• Principal Investigator: Shinji ITOH 九州大学, 大学病院, 講師 (90382423)
• Co-Investigator(Kenkyū-buntansha): 副島 雄二 信州大学, 学術研究院医学系, 教授 (30325526) ; 吉住 朋晴 九州大学, 医学研究院, 准教授 (80363373) ; 原田 昇 九州大学, 大学病院, 講師 (80419580) ; 池上 徹 九州大学, 大学病院, 講師 (80432938)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝細胞癌 / 肝内胆管癌 / フェロトーシス / 腫瘍免疫 / がん代謝 / PD-L1 / Nrf2 / VETC

Outline of Final Research Achievements

We focused on the tumor microenvironment in primary liver cancer (hepatocellular carcinoma and intrahepatic cholangiocarcinoma), and investigate the relationship with clinical data. We found novel findings on the immune response and vascular formation in the tumor microenvironment. We also elucidated inflammatory markers and preoperative imaging findings that predict the tumor microenvironment. We also identified proteins that regulate PD-L1 expression in hepatocellular carcinoma and elucidated their signaling pathways and clinical significance.
We demonstrated for the first time that administration of novel molecularly targeted agent (lenvatinib) induces ferroptosis in hepatocellular carcinoma, elucidated the significance of the FGFR4 signaling pathway, and demonstrated that the Nrf2 protein was involved in drug sensitivity.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

難治性癌の一つである原発性肝癌（肝細胞癌、肝内胆管癌）において、癌微小環境の新知見を同定し、炎症マーカーや画像所見との関係を明らかにした。原発性肝癌での微小環境を反映した新たな新規バイオマーカー候補を明らかにした。
肝細胞癌における分子標的薬におけるフェロトーシス誘導、およびその感受性の機序を明らかにした。フェロトーシスの研究により薬物療法の治療効果の向上に寄与する。