| Project/Area Number |
17K15925
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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 |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Research Collaborator |
Yamamichi Nobutake
Tomida Shuta
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | 十二指腸上皮性腫瘍 / GSEA / 網羅的遺伝子発現解析 / Wnt/βcatenin pathway / Wnt/βcatenin / 大腸腺腫 / APC mutation / 癌 / マイクロアレイ / トランスレーショナルリサーチ / 遺伝子発現 / 分析科学 |
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| Outline of Final Research Achievements |
Gene expression profiling was performed in 4 pairs of duodenal adenoma/adenocarcinomas and corresponding matched normal tissue. 626 probes consistently demonstrated over a 2-fold expression difference between tumor-normal pairs. GSEA demonstrated a strong association between duodenal adenoma/adenocarcinomas with colorectal adenomas (p<10-5) and gene expression patterns seen after APC gene knockout (p<10-5), suggesting that the Wnt/β-catenin pathway plays a crucial role in the carcinogenesis of these neoplasms. Immunohistochemical staining of an independent group of duodenal adenomas confirmed over-accumulation of β-catenin. In conclusion, precancerous duodenal adenomas and early-stage adenocarcinomas demonstrate gene expression characteristics with a strong resemblance to colorectal adenomas. The results of this study strongly suggest that up-regulation of the Wnt/β-catenin pathway is the major factor involved in the initial stages of the carcinogenesis of duodenal adenocarcinomas.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は十二指腸上皮性腫瘍の網羅的遺伝子発現解析、バイオインフォマティクス解析を通して、世界で初めて十二指腸上皮性腫瘍と大腸腺腫の類似性を示した。現在は十二指腸上皮性腫瘍に対する臨床上の治療ガイドラインも定まっておらず、今後十二指腸上皮性腫瘍に対する治療方針に寄与する結果であり、臨床的な意義が高い。また、Wnt/βcatenin pathwayが十二指腸上皮性腫瘍の形成に強く関与していることも初めて示した。最後に、十二指腸癌の発現プロファイルを明らかにすることにより、今後drug repositioningによる化学療法レジメンの予測モデル樹立に向けて基盤を形成することに成功し、意義が高い。
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