| Project/Area Number |
19KK0408
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Kobe University |
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Principal Investigator |
Fujikura Kohei 神戸大学, 医学研究科, 医学研究員 (50773751)
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| Project Period (FY) |
2019 – 2023
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
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| Keywords | 肝様腺癌 / 遺伝子変異 / 次世代遺伝子解析 |
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| Outline of Research at the Start |
肝様腺癌 (hepatoid adenocarcinoma) は、形態的にも免疫染色学的にも肝細胞様形質を呈する腺癌の亜型である。胃、膵臓、肺、子宮など様々な諸臓器での発生が報告されている。最大の特徴はリンパ節転移や肝転移が高頻度に起こる点にあり、鑑別診断や標準治療の確立が急務である。本研究では、胃原発肝様腺癌の次世代遺伝子解析を進め、分化・脱分化に関与する遺伝子の同定を目指す。
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| Outline of Final Research Achievements |
Hepatoid adenocarcinoma is a special type of adenocarcinoma that arises in tissues other than the liver but has both morphologic and functional features of hepatocellular carcinoma. The stomach is the most common site of hepatoid adenocarcinoma, with a high incidence of liver and lymph node metastases and a very poor prognosis. We are collecting surgically resected cases of primary hepatoid adenocarcinoma of the stomach and performing integrated analysis, including immunostaining, identification of driver gene mutations, expression analysis by RNA-sequencing, and examination of hepatoid differentiation of gastric cancer organoids. Our final goal is to identify the factors that cause hepatoid differentiation as well as candidate therapeutic targets. If similar carcinogenesis mechanisms can be identified in hepatoid adenocarcinoma of other organs, this may lead to a cross-disciplinary disease concept.
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| Academic Significance and Societal Importance of the Research Achievements |
肝様腺癌は胃をはじめとする様々な諸臓器で発生し、生物学的悪性度が高いことが知られている。臨床医の注目は高く、遺伝子変異、トランスクリプトーム、細胞生物学的解析を包括し、構成的に理解することは意義がある。また、欧米・アジアのいずれにおいても、肝様腺癌の発生経路に言及した報告はない。本研究成果がさらに進展すれば、病理診断の基盤構築や肝様形質に立脚した治療法が確立される可能性も考えられる。
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