Comprehensive genomic and epigenomic analyses exploring novel molecular tageted therapy for endometrial cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: University of Tsukuba
• Principal Investigator: Minaguchi Takeo 筑波大学, 医学医療系, 准教授 (40372396)
• Co-Investigator(Kenkyū-buntansha): 佐藤 豊実 筑波大学, 医学医療系, 教授 (80344886)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 子宮体癌

Outline of Final Research Achievements

We obtained epigenomic information in addition to genomic information such as protein and gene abnormalities in surgical specimens from patients with endometrial cancer who received primary surgeries at our institution. Associations of genomic and epigenomic information with clinicopathological factors and treatment outcome were comprehensively analyzed. We found that microsatellite instability may attenuate sensitivity to adjuvant chemotherapy through enhancing the immune checkpoint system, leading to poor prognosis. Adjuvant radiotherapy improved survival in patients with wild-type p53, but not in those with mutant p53, suggesting that p53 may contribute to poor prognosis through attenuating radiosensitivity. Taken together, it is suggested that chemosensitivity and radiosensitivity may be regulated by distinct mechanisms in endometrial cancer.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

子宮体癌の初回治療は現在、手術療法を基本として、臨床病理学的リスク因子の有無により術後化学療法または/および術後放射線療法を追加する。今回、ゲノム・エピゲノム異常を統合的に解析することにより、術後化学療法および術後放射線療法に対する感受性が、それぞれ異なる機序により制御されている可能性が示唆され、ゲノム・エピゲノム解析結果により術後追加治療を選択することで、子宮体癌患者の予後を更に改善できる可能性がある。今後これらの結果から、予後改善のための新たな分子標的治療や、ゲノム・エピゲノム異常に基づいた新たな管理法の開発が期待される。