| 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
|
| 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。
|
