| Project/Area Number |
18K08552
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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 55010:General surgery and pediatric surgery-related
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| Research Institution | Keio University |
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Principal Investigator |
ABE Yuta 慶應義塾大学, 医学部(信濃町), 講師 (70327526)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 胆道癌 / ゲノム医療 / 次世代シーケンサー / 肝門部胆管癌 / Precision medicin / 次世代シークエンサー / 遺伝子変異 / Precision medicine / 胆管癌 / 個別化医療 |
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| Outline of Final Research Achievements |
We analyzed all 77 radical resection sample from patients with hilar cholangiocarcinoma with successful DNA extractions. Gene sequences were sequenced using NGS to identify gene mutations. 38 gene mutations (138 mutations in total) were identified. Intrahepatic cholangiocarcinoma with hilar invasion and hilar cholangiocarcinoma derived from the large bile duct had a certain tendency for gene mutation. In addition, analysis by pathological factors revealed a significant difference between vascular infiltration and gene mutation, and lymphatic infiltration and lymph node metastasis and gene mutation. BRACA2, ERBB2, and TP53, which are common driver genes for biliary tract cancer, had the same mutation rates as previously reported, however, these were not correlate with pathological factors or prognostic factors. From our results, it was suggested that a combination of some genetic abnormalities could be a predictor of prognosis.
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| Academic Significance and Societal Importance of the Research Achievements |
肝門部領域胆管癌は非常に予後不良な疾患である。それは高い悪性度と手術の高侵襲のためであり、その治療成績向上には手術治療と組み合わせた効果的な薬物治療の開発が必要とされている。一方肝門部領域胆管癌は欧米では発生頻度が低いため研究が盛んではない。つまりその希少性から大規模研究が難しく新規治療薬の開発や臨床応用が非常に遅れている。この背景において本研究では次世代シークエンサーを用いた癌遺伝子パネルを用いて肝門部領域胆管癌の遺伝子解析を行い、特徴的な変異パターンを解析し病理組織像や患者予後と遺伝子異常にある一定の相関を知ることができた。これは今後の新たな治療効果判定や新規治療薬開発の基礎となり得る。
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