Characterizetion of TFFI2, a novel diagnosis biomarker for ovarian cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K07147
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: National 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
• Keywords: 卵巣癌 / 明細胞癌 / バイオマーカー / TFPI2 / 糖鎖

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.

Free Research Field

プロテオーム解析

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。