| Project/Area Number |
18K07024
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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 49020:Human pathology-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 胆管癌 / バイオマーカー / 早期診断 / PDGF-D / Matriptase / 腫瘍分化度 / 肝外胆管癌 / matriptase / 癌間質 / 胆道癌 / 癌関連線維芽細胞 / 無再発生存期間 / 全生存期間 / 診断マーカー / 分子サブタイピング |
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| Outline of Final Research Achievements |
To establish integrated molecular subtyping of biliary tract cancer, we investigated platelet-derived growth factor-D (PDGF-D), a receptor-type tyrosine kinase, and matriptase, a protease. We found that tumors with high expression of matriptase in the tumor stroma have a poor prognosis. We also proposed a new histological scoring system for extrahepatic cholangiocarcinoma that can predict prognosis by taking tumor heterogeneity into account. Furthermore, in order to select useful markers for improving the diagnostic accuracy of biopsy and cytological diagnosis of cholangiocarcinoma, 10 antibodies were examined by immunohistochemical staining. In terms of sensitivity and positive diagnosis rate, S100P and IMP3 performed relatively well. On the other hand, p53, S100A4, and Maspin had low sensitivity (less than 50%) but specificity (100%), and were considered useful for diagnosis in some cases.
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| Academic Significance and Societal Importance of the Research Achievements |
胆道癌は予後不良な癌腫の一つで、有効な早期診断マーカーや分子標的治療などもまだない。腫瘍の完全切除が為されれば、ある程度の予後改善が見込めるが、解剖学的に切除範囲が制限されることが多く、全体としては依然として大幅な予後改善が困難な腫瘍である。今回の研究により胆管癌の生検診断自体に役立つマーカー（S100PとIMP3）を明らかにした。また、matriptaseという物質が癌の間質で高発現していることを明らかにしたことや腫瘍の不均一性を考慮して予後を予測できる新たなスコアシステムの考案により生検標本などでも症例の層別化を行える可能性を示した。
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