Nuclear translocation of hypoxia related factors and examination of its inhibitory effect: individualization from the therapeutic viewpoint

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08355
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Saitama Medical University
• Principal Investigator: Yasuda Masanori 埼玉医科大学, 医学部, 教授 (50242508)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 低酸素誘導因子 / ヒストン脱アセチル化酵素 / 卵巣癌 / 卵巣明細胞癌 / ARID1A

Outline of Final Research Achievements

In ovarian clear cell carcinomas, the single-nucleotide polymorphisms (C1772T) of hypoxia inducible factor (HIF)-1α is more frequent than in healthy group and other carcinomas, but it does not affect patient prognosis or its protein expression. Immunohistochemical expression of HIF-1α and its regulator histone deacetylase (HDAC)6 do not correlate with prognosis in ovarian clear cell canrcioma patients without ARID1A mutation, but with ARID1A mutation Significantly reduced survival time. In clear cell ovarian carcinomas, we found that HIF-1α and HDAC6 could be prognostic factors and therapeutic targets, and that ARID1A could be a biomarker.

Free Research Field

婦人科腫瘍病理学

Academic Significance and Societal Importance of the Research Achievements

卵巣癌の中でも、卵巣明細胞癌は既存の化学療法に抵抗性とされ、有効な化学療法の開発が望まれている。我々の研究は卵巣明細胞癌の主要な遺伝子変異であるARID1Aをバイオマーカーとして、HIF-1αやHDAC6が予後予測因子や治療標的となりえることを見出した。卵巣癌においても組織型や遺伝子変異に応じて治療を個別化するべきと考えられる。