| Project/Area Number |
17K16521
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
Shimizu Dai 九州大学, 大学病院, 医員 (50723037)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 胃癌 / 肝転移 / FRAS1 / Transcriptome解析 / 個別化治療 / 次世代シーケンサー |
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| Outline of Final Research Achievements |
Recurrence pattern-specific transcriptome analysis was performed to identify liver metastasis-associated genes, and consequntly FRAS1 was identified as a liver metastasis-associated gene. The proliferation of FRAS1 knockout cell line (FRAS1-KO) was attenuated compared with that of the parental cell line through increased caspase activity and alteration of the cell cycle. FRAS1-KO cells exhibited increased responsiveness to oxygen stress and diminished stemness, invasiveness, and migration. Mouse models of GC revealed decreases in tumor formation and generation of metastasis by FRAS1-KO cells. Moreover, the cumulative rate of liver recurrence was significantly increased in patients with GC with high levels of FRAS1 expression. FRAS1 contributes to the malignant potential of GC, metastasis, and liver recurrence and may therefore serve as a predictive marker or a target for treating liver metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
胃癌肝転移は有効な根治治療が確立されておらず致死的な病態である。胃癌が肝転移をきたすメカニズムや、肝転移を誘導する分子の解明は、胃癌の肝転移予測ならびに治療法の開発に不可欠である。今回我々はFRAS1を胃癌肝転移関連分子として同定し、その遺伝子発現が胃癌細胞の悪性度に関与することを明らかにした。また、胃癌患者コホートにおいてFRAS1発現は独立した肝転移予測因子であった。さらに動物実験では、FRAS1発現が肝転移に特徴的に関与する可能性を示した。今後、FRAS1が胃癌肝転移の予測マーカーならびに治療標的となる事が期待される。
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