The study of novel diagnosis and treatment for endometrial cancer targeting aberrant DNA methylation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: Banno Kouji 慶應義塾大学, 医学部(信濃町), 准教授 (70265875)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 子宮内膜癌 / 異常メチル化 / miR-663a / メトホルミン

Outline of Final Research Achievements

(1) Based on genome-wide bisulfite sequencing, peripheral blood cells(PBCs) DNA in M-H cases had significant hypermethylation in the miR-663a promoter region, compared to U cases (meth. Diff. > 25%, q-value < 0.01). Consistent with this methylation status, miR-663a expression was lower in M-H PBCs than in U PBCs. DNMTs expression levels in M-H endometrial cancer were higher than those in U endometrial cancer.
(2) Metformin had a dose-dependent anticancer effect on endometrial cancer cell lines. Moreover, the combined treatment also caused lower cell viability.The microarray analysis indicated that EDN2 expression was upregulated in cells subject to the combined treatment. EDN2 expression was upregulated in each cell line upon treatment with a demethylating agent.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

（１）腫瘍部において異常高メチル化を認める子宮内膜癌患者は、正常細胞においても一部の遺伝子に異常メチル化を認めた。正常細胞における異常メチル化が癌のフェノタイプに寄与する可能性が示唆された。今後、癌の予防や早期発見に繋がる結果と考えられる。
（２）本研究において抗癌剤としての有用性を検討した薬剤は、既に他の疾病に対し処方されているため、安全性や副作用の情報が蓄積されている。新規の抗癌剤開発にかかる時間短縮・費用削減など、臨床応用されれば意義は大きいと考えられる。