Epithelial- Mesenchymal transition and genetic mutation in Lymph node metastasis in extrahepatic cholalngiocarcinoma
| Project/Area Number |
17K10684
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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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| Research Field |
Digestive surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平野 聡 北海道大学, 医学研究院, 教授 (50322813)
土川 貴裕 北海道大学, 大学病院, 講師 (50507572)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肝外胆管癌 / 肝門領域胆管癌 / 遠位胆管癌 / EMT / リンパ節転移 / Tumor Budding / 遺伝子変異 / NGS / tumor budding / 肝門部領域胆管癌 / lymph node metastasis / MET / 消化器外科学 / 胆道外科学 |
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| Outline of Final Research Achievements |
To clarify the mechanism of lymph node metastasis in extrahepatic cholangiocarcinoma (EHCC), we performed studies as follows: 1) the association between the number of tumor budding (TB) at the invasive area and clinicopathological factors, postoperative prognosis. 2)associations between the number of TB and expression of immunohistochemical staining of proteins associated with epithelial-mesenchymal transition (EMT). 3) gene mutations in primary tumor and lymph node metastasis by using next generation sequencer. Results. 1) There were significantly associations between high number grade of TB and invasive natural factors and adverse prognosis. 2) There was significantly correlation between high staining of EMT pattern and higher number of TB. 3) There was not characteristic mutation of lymph node metastasis. However, mutations in primary and lymph node were almost same.
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| Academic Significance and Societal Importance of the Research Achievements |
１）の結果から癌細胞がTBの形態をとることが転移のプロセスで重要であると示唆された。また、TBはEMTの形態学的表現形であることが推測されたが、2)の結果はこれを強く支持する結果と言える。しかし、3)の結果からはリンパ節転移に特化した遺伝子変異は同定できなかったことから、EMTは遺伝子変異だけで説明できるものでないことが示唆された。さらに３）の結果から肝外胆管癌の遺伝子変異は症例ごとに異なっているが、転移巣においても原発と変異がほぼ同等であることから、症例ごとに原発巣における遺伝子変異を調べることにより、再発転移巣の治療ターゲットとなる遺伝子変異を推測することが将来的に可能になると考えられた。
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Report
(4 results)
Research Products
(4 results)
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[Journal Article] Impact of Tumour Budding Grade in 310 Patients Who Underwent Surgical Resection for Extrahepatic Cholangiocarcinoma.2019
Author(s)
Ogino M, Nakanishi Y, Mitsuhashi T, Hatanaka Y, Amano T, Marukawa K, Nitta T, Ueno T, Ono M, Kuwabara S, Yamada T, Hirano S.
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Journal Title
Histopathology.
Volume: 「印刷中」
Issue: 6
Pages: 861-872
DOI
Related Report
Peer Reviewed / Open Access
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