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Characterizetion of TFFI2, a novel diagnosis biomarker for ovarian cancer

Research Project

Project/Area Number 16K07147
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor diagnostics
Research InstitutionNational Institute of Health Sciences

Principal Investigator

Arakawa Noriaki  国立医薬品食品衛生研究所, 医薬安全科学部, 主任研究官 (60398394)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords卵巣癌 / 明細胞癌 / バイオマーカー / TFPI2 / 糖鎖 / 卵巣がん / 明細胞がん / 卵巣明細胞癌 / LacdiNAc / LacNAc / プラスミン / 癌 / 蛋白質 / プロテオーム
Outline of Final Research Achievements

Tissue factor pathway inhibitor 2 (TFPI2) is a serum biomarker candidate for ovarian clear cell carcinoma (OCCC), a highly lethal histological subtype of ovarian cancer. TFPI2 is also known to be a placental specific Kunitz-type protease inhibitor that is exclusively expressed in the blood of pregnant women. In this study, to clarify the difference between TFPI2 produced from OCCC and placenta, the glycan structure of TFPI2 from cultured placental cells and OCCC cell lines were analyzed by mass spectrometry. The analysis revealed that OCCC-derived TFPI2 has bi-antennary complex type glycans with the LacdiNAc structure, unlike the placental cell-derived TFPI2 that preferentially attaches to bi-, or tri-antennary glycans with the LacNAc structure. Similar results were confirmed in the analysis of serum from pregnant women. This finding may allow the development of a new method for highly specific detection of OCCC.

Academic Significance and Societal Importance of the Research Achievements

卵巣癌の組織型の中でも、卵巣明細胞癌(OCCC)は、抗がん剤に対する抵抗性が高く予後が悪い。TFPI2はOCCCの血清診断に有用なバイオマーカーとして期待されているタンパク質であるが、妊婦の血清中でも増加するため、妊婦とOCCC患者を見分けることができない。本研究では、TFPI2に結合している糖鎖を解析し、妊婦胎盤で作られるTFPI2とOCCCが作るTFPI2の違いを明らかにした。本研究で得られた知見は、診断特異性の高い卵巣癌診断法の開発に役立つと期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2017 2016

All Presentation (1 results) Patent(Industrial Property Rights) (1 results)

  • [Presentation] 卵巣明細胞癌と妊婦胎盤が賛成するTFPI2の糖鎖構造比較解析2016

    • Author(s)
      荒川憲昭、岡部美妃、高倉大輔、平野久、川崎ナナ
    • Organizer
      日本プロテオーム学会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-28
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 疾患特異的な組織因子経路インヒビター2の糖鎖構造の利用2017

    • Inventor(s)
      荒川憲昭、高倉大輔、川崎ナナ、大竹則久
    • Industrial Property Rights Holder
      横浜市立大学・東ソー
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-022398
    • Filing Date
      2017-02-09
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2023-01-30  

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