2022 Fiscal Year Final Research Report
Identification of Cancer Biomarker and Novel Therapeutic Molecutargets by Elucidation of Metabolism in IPMN of Pancreas
| Project/Area Number |
20K09039
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
猪股 雅史 大分大学, 医学部, 教授 (60315330)
岩下 幸雄 大分大学, 医学部, 客員研究員 (60534203)
平下 有香 大分大学, 医学部, 病院特任助教 (70771955)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 膵管内乳頭粘液性腫瘍 / 糖代謝 / FDG-PET / mTORC1 |
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| Outline of Final Research Achievements |
We plan to identify biomarkers for malignant transformation and new therapeutic target by investigating the role of S6 phosphorylation and the significance of glucose metabolic changes in IPMN.
GLUT1 expression increased with carcinogenesis from adenoma to adenocarcinoma, and glucose metabolism changed at the same time. Clinically, there was an association between IPMN carcinogenesis and FDG-PET, and it was useful to diagnose as adenoma or adenocarcinoma with a sensitivity of 85% and a specificity of 96%. During IPMN carcinogenesis, mTORC1 was activated in adenocarcinoma, and mTORC1 was associated with glucose metabolism.
Although IPMN organoids can be created, the success rate was low. They were not useful to identify therapeutic targets. Suppression of mTORC1 activity leads to suppression of proliferation in pancreatic cancer cells, and pS6 and GLUT1 are not correlated with prognosis in the clinical cases. mTORC1 activity was considered to have a strong effect on carcinogenesis.
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| Free Research Field |
膵腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
IPMNは手術時期決定のためには腺腫と腺癌の鑑別が重要であり、今回その鑑別のためのバイオマーカーの同定を行った。発癌に伴うGLUT1発現の亢進が明らかとなり、FDG-PETはIPMNの癌化を診断する有用な検査法であることがわかった。また、「有効な治療法の確立」のため、mTORC1活性に伴う浸潤メカニズムの解明と治療標的の同定を行い、mTORC1活性抑制ががんの増殖抑制につながることがわかり、今後実際のIPMNにおける治療のターゲットの一因子となりうる。
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