| Project/Area Number |
16K09382
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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 |
Gastroenterology
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| Research Institution | Kindai University |
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Principal Investigator |
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| Research Collaborator |
KUDO Masatoshi
KAIDO Toshimi
TANAKA Shinji
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肝細胞癌 / 転移 / ゲノム / エピゲノム / クロモゾーム / 化学療法 / 遺伝子変異 / メチローム / 分子分類 / 転移再発 / 分子スコア / アジュバント療法 / 遺伝子 |
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| Outline of Final Research Achievements |
We clarify molecular features of aggressive HCC, and establish a molecular scoring system that predicts metastasis after curative treatment. In total, 125 HCCs were examined for genome methylome and chromosomal analyses; molecular subclasses and risk score were determined. Next, HCC patients who underwent liver transplantation were analyzed for molecular risk score and metastatic recurrence; survival analyses were validated using a dataset of 376 HCC cases from the Cancer Genome Atlas (TCGA). Molecular risks, that consisted with presence of TP53 mutation, high FAL, global hypomethylation, and absence of CTNNB1 mutation were noted to predict shorter recurrence-free survival in both liver transplantation cohort (p = 0.0090 by log-rank test). and TCGA cohort (p = 0.0076). We concluded that molecular score could predict metastatic recurrence after curative treatments, and could be a marker for considering systemic therapy for HCC patients.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、肝癌の薬物療法は急速に発展し、肝動脈塞栓術(TACE)の奏効率に近づいている。一方、TACEは肝機能を悪化させるため、TACE後の転移再発のリスクの高い群では薬物療法を先行させるべきとの考えが広がっている。しかし、現在、TACE後の転移再発を予測することは困難である。さらに、肝切除においても、転移再発のリスクの高い群ではアジュバント、ネオアジュバントとしての薬物療法の適応を考慮すべきである。本研究成果は、肝癌転移再発の高リスク群を同定する分子スコアの開発であり、肝癌のマネージメントにおける意義は大きい。
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