2023 Fiscal Year Final Research Report
Cytoplasmic EBP50 and elevated PARP1 are unfavorable prognostic factors in ovarian clear cell carcinoma
| Project/Area Number |
20K07397
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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 49020:Human pathology-related
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 卵巣明細胞癌 / プロテオーム / EBP50 / PARP1 / 抗癌剤耐性 |
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| Outline of Final Research Achievements |
Patients with ovarian clear cell carcinoma (OCCC) experience frequent recurrence, which is most likely due to chemoresistance. We used shotgun proteomics analysis and identified upregulation of EBP50 in recurrent OCCC samples. Abrogation of resistance following knockdown of EBP50 was accompanied by increased apoptotic cells. We found that PARP1, which is involved in DNA damage detection and repair, binds to EBP50 through its PDZ1 domain. Cisplatin treatment of cells expressing EBP50 increased nuclear PARP1 expression, whereas knockdown of EBP50 cells decreased PARP1 expression and activity following Cisplatin treatment. Finally, OCCC patients with a combination of EBP50 and high PARP1 score had worst the prognosis for overall and progression-free survival.
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| Free Research Field |
分子病理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で用いたホルマリン固定パラフィン包埋検体のショットガンプロテオミクス法による網羅的解析は、我々のグループ独自の解析手法である。本法によりOCCCの再発・予後を規定する候補因子としてEBP50を見出し、国内外を通じて、OCCCにおけるEBP50発現とその機能解析は殆ど手付かずの状態であり、極めて独自性の高い研究である。小分子化合物等を用いたEBP50シグナル系阻害による新規治療法の分子基盤を築くことができる。特に、本分子を標的とした治療法は、再発例や標準治療に抵抗性を示すOCCCに対しても有効であることが想定され、患者予後改善に著しく貢献できることが期待できる。
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