Analysis of epigenome and metabolic phenotypes in Thai liver fluke-associated cholangiocarcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 20KK0185
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Kumamoto University
• Principal Investigator: NAKAO MITSUYOSHI 熊本大学, 発生医学研究所, 教授 (00217663)
• Co-Investigator(Kenkyū-buntansha): 長岡 克弥 熊本大学, 病院, 助教 (00759524) ; 古賀 友紹 熊本大学, 発生医学研究所, 講師 (30615092)
• Project Period (FY): 2020-10-27 – 2024-03-31
• Keywords: 胆管細胞癌 / エピゲノム / 遺伝子 / 代謝 / 高血糖 / 乳酸アシドーシス

Outline of Final Research Achievements

It has been reported that in certain regions of Thailand, there are many cases of cholangiocarcinoma (CCA) closely related with parasites and diabetes. The purpose of this study was to elucidate the metabolic characteristics of CCA cells from the perspective of epigenomic regulation, and to approach the development of cancer diagnosis and control methods based on the molecular pathology. Metabolism and epigenome reprogramming in cancer cells have attracted attention, but many aspects of their molecular mechanisms remain unclear. In this study, we looked at cancer metabolism from a new perspective: the switching of metabolic strategies by the epigenome mechanism. We aimed to elucidate the biological significance of tumors by elucidating the mechanisms by which high glucose, oxidative stress, and lactic acidosis in the microenvironment promote metabolic and phenotypic remodeling in cholangiocarcinoma cells.

Free Research Field

腫瘍学およびその関連分野

Academic Significance and Societal Importance of the Research Achievements

タイ国の特定の地域では、寄生虫による胆管細胞癌（CCA）と糖尿病の合併例が多いことが報告されている。国際共同研究として、エピゲノム制御の観点からCCAの代謝特性を解明し、その分子病態に基づいた癌の診断・制御法の開発に迫ることを目的とした。胆管癌細胞において、微小環境の高グルコースと酸化ストレス、乳酸アシドーシスが代謝型と表現型のリモデリングを促進する機序を明らかにした。熊本大学とコンケーン大学の大学間交流協定とDouble Degree Program、大学院博士課程学生の受入・学位取得を実施した。