Cellular deconvolution analysis of hepatocellular carcinoma based on the systemic epigenomic profiles
Project/Area Number |
18K07963
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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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)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 肝がん / DNAメチル化 / 微小環境 / 肝癌 / 細胞不均一性 / 一細胞解析 / 肝細胞癌 |
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.
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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。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Sex differences in oncogenic mutational processes2020
Author(s)
Li Constance H.、PCAWG Tumour Subtypes and Clinical Translation、Prokopec Stephenie D.、Sun Ren X.、Yousif Fouad、Schmitz Nathaniel、Boutros Paul C.、PCAWG Consortium
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Journal Title
Nature Communications
Volume: 11
Issue: 1
Pages: 4330-4330
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A novel sensitive detection method for DNA methylation in circulating free DNA of pancreatic cancer2020
Author(s)
Shinjo K, Hara K, Nagae G, Umeda T, Katsushima K, Suzuki M, Murofushi Y, Umezu Y, Takeuchi I, Takahashi S, Okuno Y, Matsuo K, Ito H, Tajima S, Aburatani H, Yamao K, Kondo Y.
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Journal Title
PLoS One
Volume: 15
Issue: 6
Pages: 0233782-0233782
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Defined lifestyle and germline factors predispose Asian populations to gastric cancer2020
Author(s)
Suzuki A, Katoh H, Komura D, Kakiuchi M, Tagashira A, Yamamoto S, Tatsuno K, Ueda H, Nagae G, Fukuda S, Umeda T, Totoki Y, Abe H, Ushiku T, Matsuura T, Sakai E, Ohshima T, Nomura S, Seto Y, Shibata T, Rino Y, Nakajima A, Fukayama M, Ishikawa S, Aburatani H.
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Journal Title
Science Advances
Volume: 6
Issue: 19
Pages: 9778-9778
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Two distinct modes of DNMT1 recruitment ensure stable maintenance DNA methylation2020
Author(s)
A. Nishiyama, C. Mulholland, S. Bultmann, S. Kori, A. Endo, Y. Saeki, W. Qin, C. Trummer, Y. Chiba, H. Yokoyama, S. Kumamoto, T. Kawakami, H. Hojo, G. Nagae, H. Aburatani, K. Tanaka, K. Arita, H. Leonhardt, M. Nakanishi
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Journal Title
Nat. Commun.
Volume: 11
Issue: 1
Pages: 1222-1222
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells2019
Author(s)
Nakato R, Wada Y, Nakaki R, Nagae G, Katou Y, Tsutsumi S, Nakajima N, Fukuhara H, Iguchi A, Kohro T, Kanki Y, Saito Y, Kobayashi M, Izumi-Taguchi A, Osato N, Tatsuno K, Kamio A, Hayashi-Takanaka Y, Wada H, Ohta S, Aikawa M, Nakajima H, Nakamura M, McGee RC, Heppner KW, Kawakatsu T, Genno M, Yanase H, Kume H, et al.
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Journal Title
Epigenetics & Chromatin
Volume: 12
Issue: 1
Pages: 77-77
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Integrated molecular profiling of juvenile myelomonocytic leukemia2018
Author(s)
Murakami N, Okuno Y, Yoshida K, Shiraishi Y, Nagae G, Suzuki K, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Ito M, Hirayama M, Watanabe A, Ueno T, Kojima S, Aburatani H, Mano H, Miyano S, Ogawa S, Takahashi Y, Muramatsu H
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Journal Title
Blood
Volume: 131
Issue: 14
Pages: 1576-1586
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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