Cellular deconvolution analysis of hepatocellular carcinoma based on the systemic epigenomic profiles

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07963
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nagae Genta 東京大学, 先端科学技術研究センター, 講師 (10587348)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肝がん / DNAメチル化 / 微小環境

Outline of Final Research Achievements

We established and validated a method to accurately quantify the composition of cancerous and non-cancerous cells comprising the clinical liver cancer tissues. Cell deconvolution was performed in a mixed linear model to estimate the compositional ratio of various cells and the pure methylation rate of individual cells. When implemented in a multi-omics analysis of liver clinical tissues, it was found that the percentage of tumor cell fraction estimated by LUMP method were well correlated with the result of epithelial cell fraction in this approach. The subgroups (E4) with fewer tumor cell components identified by hierarchical clustering of bulk methylation data tended to be dominated by CD4+ and CD8+ T cells, monocytes and macrophage-like cells.

Free Research Field

ゲノム医学

Academic Significance and Societal Importance of the Research Achievements

肝癌組織の一部には間質の増生や炎症細胞浸潤の高いものも存在するが、こうした症例はしばしば大規模プロジェクトの対象外とされてきたため、ドライバー変異を含む分子プロファイルとの関係が明らかでない。本研究課題で開発した推定法により、こうした症例も含めたあらゆる肝癌組織の分子プロファイルを対象にしうると考えられた。また、非癌細胞の構成比率を明らかにすることで、癌細胞の純粋なメチル化プロファイルを逆算することも可能となり、新たなエピゲノム制御異常が解明できる可能性がある。