Identification of novel biomarkers for high-risk endometrial cyst of the ovary

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09236
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kyorin University
• Principal Investigator: Kobayashi Yoichi 杏林大学, 医学部, 教授 (90205493)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 子宮内膜症性嚢胞 / 薬剤抵抗性 / 黄体ホルモン / アズロシジン / 炎症性サイトカイン

Outline of Final Research Achievements

We have identified some proteins from endometrial cyst fluid those were candidate as resistant against Dienogest (DNG), therapeutic drug for endometriosis, by proteomics analysis. One of the, we focused on azurocidin (AZU), and analyzed its characterizations. We revealed that AZU promotes expression of inflammatory cytokines those exacerbate endometriosis, and AZU suppresses effect of DNG. One of the mechanisms, we also revealed AZU promotes expression of estrogen receptor and progesterone-B receptor those both exacerbate endometriosis. Then AZU shows inhibitory effect for DNG via hormone receptors. In clinical samples, concentrations of serum and urine AZU was significantly higher in the patients with DNG-resistant compared to others patients. In conclusions, it revealed that AZU is associated with exacerbation and drug-resistance, then AZU could be a novel biomarker for drug-resistant, and it could be useful for determination of therapeutic strategy.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

卵巣内膜症性嚢胞は月経困難症をきたし女性のQOLを損なうばかりではなく、不妊症の原因にもなる。治療法としては薬物療法と手術療法に大別されるが、はっきりとした治療指針は確立されていない。本研究で新規バイオマーカーにより薬剤抵抗性の患者を拾い上げることができれば、治療方針の決定に大きく寄与することが期待され、また女性のQOL向上による社会的生産性の増加や、大きな意味では少子化対策の一環ともなり得る。また未だ癌化との関連性は明らかではないが、薬物抵抗性ということが判明すればより積極的な手術療法による病巣の除去により、将来的な癌化のリスクを減少させることも期待できる。