Analysis of the molecular mechanism by which FGFR3IIIc promotes esophageal cancer progression.
| Project/Area Number |
17K10611
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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 | Kyoto Sangyo University |
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Principal Investigator |
SEO Misuzu 京都産業大学, 生命科学部, 教授 (60211223)
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| Co-Investigator(Kenkyū-buntansha) |
上田 修吾 公益財団法人田附興風会, 医学研究所 第1研究部, 研究主幹 (80372580)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 食道がん / 線維芽細胞増殖因子受容体3 / がん悪性化 / 抗がん剤耐性 / 選択的スプライシング / 線維芽細胞増殖因子受容体 / 予後 / フルオロウラシル / MEK阻害剤 / FGFR3IIIc / スプライシング / ドセタキセル / 全生存期間 / リン酸化型AKT / 生存期間 / 転移 / 早期発見 |
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| Outline of Final Research Achievements |
Esophageal cancer patients (EC) have poor prognosis among all cancers. In this study, clinical significance of the increased expression of an alternatively spliced isoform of Fibroblast Growth Factor Receptor 3, FGFR3IIIc, in the specimens of esophageal cancer patients was examined by analyzing the immunohistochemical staining. As a result, the FGFR3IIIc expression levels in the EC were higher than those in the normal esophagus epithelium (p<0.01). In addition, the ratio of FGFR3IIIc expression levels in the EC patients was negatively correlated with overall survival (OS) (r=-0.436). OS in the EC patients with higher expression levels of FGFR3IIIc was shorter than that in those with lower expression levels of FGFR3IIIc (P<0.01). In addition, overexpression of FGFR3IIIc in EC cells increased the resistance (IC50) for anti-cancer drugs such as fluorouracil and Docetaxel. In conclusion, FGFR3IIIc has the potential to be a molecular target for EC therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
日本における食道がん患者の5 年生存率は約40%と低く、他の消化器がんの60%と比較して予後が悪いことから、食道がん患者の予後が悪いメカニズムを解明することが、効果的な治療薬の開発に重要である。線維芽細胞増殖因子受容体3(FGFR3)はチロシンキナーゼ型受容体で、がんの悪性化に働く。本研究で、FGFR3IIIcの発現が高いほど、食道がん患者の生存期間が短くなることが証明された。さらに、FGFR3IIIcが発現することで標準治療薬である抗がん剤への薬剤耐性も獲得し、再発の可能性が高くなることが分かった。FGFR3IIIcの発現または機能を阻害することができれば、食道がん患者の治療に大きく役立つ。
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Report
(4 results)
Research Products
(8 results)
