| Project/Area Number |
22K15544
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | VETC / mTOR / Ang-2 / 肝細胞癌 |
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| Outline of Research at the Start |
肝細胞癌の転移や腫瘍免疫回避にAng2、VEGF、Rac、DOCK1が関与する可能性はあるが、その詳細は未だ不明な部分が多く、その解明は急務であると思われる。本研究では、肝細胞癌における転移の分子機構および腫瘍免疫回避機構を解明し、その中心的役割を担う遺伝子を制御する薬剤を開発して免疫チェックポイント阻害剤の奏功率を向上させることを目的とする。
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| Outline of Final Research Achievements |
This study aimed to elucidate the molecular mechanisms of metastasis and tumor immune evasion in hepatocellular carcinoma (HCC). Cases of HCC patients who underwent hepatectomy or living donor liver transplantation at our institution were evaluated for the expression of VETC, Ang-2, and mTOR by immunohistochemical staining. Among the patients, those who were VETC-positive showed a significantly higher rate of mTOR positivity compared to VETC-negative patients, and the expression of Ang-2 was significantly higher in the mTOR-positive group than in the mTOR-negative group. Among cases of HCC recurrence after living donor liver transplantation, the expression of mTOR was significantly higher in recurrent lesions that were positive for VETC compared to those that were negative for VETC. Additionally, mTOR expression was found to be higher in primary and recurrent lesions that were VETC-positive compared to those that were VETC-negative.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により肝細胞癌に対して生体肝移植術を施行した患者においてmTOR発現は、VETC陰性の原発巣および再発病変よりもVETC陽性の原発巣および再発病巣で高いことが明らかとなった。生体肝移植後のエベロリムスの使用がVETC陽性の肝細胞癌患者における腫瘍再発を予防または減少させる可能性があることが示唆され、生体肝移植術を施行した肝細胞癌患者の治療に重要な意味を持つ。
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