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Risk estimation of pancreatic adenocarcinomas based on epigenome-wide association study

Research Project

Project/Area Number 16H02472
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor diagnostics
Research InstitutionKeio University

Principal Investigator

Kanai Yae  慶應義塾大学, 医学部(信濃町), 教授 (00260315)

Co-Investigator(Kenkyū-buntansha) 山地 太樹  国立研究開発法人国立がん研究センター, 社会と健康研究センター, 室長 (10466203)
新井 恵吏  慶應義塾大学, 医学部(信濃町), 講師 (40446547)
伊藤 秀美  愛知県がんセンター(研究所), がん情報・対策研究分野, 分野長 (90393123)
Research Collaborator YOSHIDA Teruhiko  
GOTOH Masahiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥46,670,000 (Direct Cost: ¥35,900,000、Indirect Cost: ¥10,770,000)
Fiscal Year 2018: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2017: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2016: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
Keywordsエピゲノム / エピゲノムワイド関連解析 (EWAS) / 膵がん / DNAメチル化 / エピゲノムワイド関連解析 / リスク診断
Outline of Final Research Achievements

The aim of this study was to establish the criteria for risk estimation of pancreatic cancer using blood samples based the research strategy of epigenome-wide association study. Using genome-wide DNA methylation analysis, 46,924 CpG sites showing significant differences of DNA methylation levels between blood samples of individuals who will suffer pancreatic cancer later and age and sex-matched control blood samples and simultaneously showing such differences of DNA methylation levels between pancreatic cancer tissue and normal pancreatic tissue samples were identified. Many of genes showing such DNA methylation alterations in both blood and tissue samples participated in stemness and/or cell proliferation and were potential tumor-related genes. These data indicated that cancer-prone DNA methylation profile can be detected even in blood samples and revealed the feasibility of pancreatic cancer risk estimation using blood samples during health checkup.

Academic Significance and Societal Importance of the Research Achievements

本研究で同定したリスク診断マーカーCpG部位の、DNAメチル化率の診断閾値を組み合わせることによって、健診等の血液検査によって将来の膵がんの発生リスクを予測するための診断基準を確立できる見込みである。確立した膵がん発生リスク診断基準について、適切に知財を確保する。さらに、研究代表者等が企業と共同研究開発し既に特許の成立している、健診機関にも普及が容易で血液検査に適した、高速液体クロマトグラフィーを基盤とするDNAメチル化診断システムに適合させ、キット化する。これにより、予防先制医療が当然のこととなる近い将来に、発がんリスク診断と介入予防の社会実装を図れると期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (41 results)

All 2019 2018 2017 2016 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 11 results,  Acknowledgement Compliant: 2 results) Presentation (21 results) (of which Int'l Joint Research: 3 results,  Invited: 14 results) Remarks (3 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 2 results)

  • [Journal Article] Genome-wide DNA methylation profile of early-onset endometrial cancer: Its correlation with genetic aberrations and comparison with late-onset endometrial cancer.2019

    • Author(s)
      Makabe T, Arai E, Hirano T, Ito N, Fukamachi Y, Takahashi Y, Hirasawa A, Yamagami W, Susumu N, Aoki D, Kanai Y.
    • Journal Title

      Carcinogenesis

      Volume: 印刷中 Issue: 5 Pages: 1-13

    • DOI

      10.1093/carcin/bgz046

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Steatotic and nonsteatotic scirrhous hepatocellular carcinomas reveal distinct Clinicopathological features.2019

    • Author(s)
      Hatano M, Ojima H, Masugi Y, Tsujikawa H, Hiraoka N, Kanai Y, Shimada K, Shinoda M, Sakamoto M.
    • Journal Title

      Hum Pathol

      Volume: 印刷中 Pages: 222-232

    • DOI

      10.1016/j.humpath.2018.11.024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research: Standard operating procedures based on empirical analyses.2018

    • Author(s)
      Kanai Y, Nishihara H, Miyagi Y, Tsuruyama T, Taguchi K, Katoh H, Takeuchi T, Gotoh M, Kuramoto J, Arai E, Ojima H, Shibuya A, Yoshida T, Akahane T, Kasajima R, Morita KI, Inazawa J, Sasaki T, Fukayama M, Oda Y.
    • Journal Title

      Pathology International

      Volume: 68 Issue: 2 Pages: 63-90

    • DOI

      10.1111/pin.12631

    • NAID

      120007134466

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenome mapping of human normal purified hepatocytes: personal epigenome variation and genome-epigenome correlation.2018

    • Author(s)
      Arai E, Miura F, Totoki Y, Yamashita S, Tian Y, Gotoh M, Ojima H, Nakagawa H, Takahashi Y, Nakamura H, Hama N, Kato M, Kimura H, Suzuki Y, Ito T, Shibata T, Kanai Y.
    • Journal Title

      Epigenomics

      Volume: 10 Issue: 7 Pages: 955-979

    • DOI

      10.2217/epi-2017-0111

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Feasibility of methylome analysis using small amounts of genomic DNA from formalin-fixed paraffin-embedded tissue.2018

    • Author(s)
      Ohara K, Arai E, Takahashi Y, Fukamachi Y, Ito N, Maeshima AM, Fujimoto H, Yoshida T, Kanai Y.
    • Journal Title

      Pathol Int

      Volume: 68 Issue: 11 Pages: 633-635

    • DOI

      10.1111/pin.12716

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application.2018

    • Author(s)
      Yotani T, Yamada Y, Arai E, Tian Y, Gotoh M, Komiyama M, Fujimoto H, Sakamoto M, Kanai Y.
    • Journal Title

      Cancer Sci

      Volume: 109 Issue: 5 Pages: 1690-1700

    • DOI

      10.1111/cas.13566

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system2018

    • Author(s)
      Saito Yoshimasa、Nakaoka Toshiaki、Muramatsu Toshihide、Ojima Hidenori、Sukeda Aoi、Sugiyama Yuko、Uchida Ryoei、Furukawa Ryo、Kitahara Aya、Sato Toshiro、Kanai Yae、Saito Hidetsugu
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2821-2821

    • DOI

      10.1038/s41598-018-21121-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenome mapping of human normal purified hepatocytes: Personal epigenome variation and genome-epigenome correlation.2018

    • Author(s)
      Arai E, Miura F, Totoki Y, Yamashita S, Tian Y, Gotoh M, Ojima H, Nakagawa H, Takahashi Y, Nakamura H, Hama N, Kato M, Kimura H, Suzuki Y, Ito T, Shibata T, Kanai Y.
    • Journal Title

      Epigenomics

      Volume: 未定

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genes involved in development and differentiation are commonly methylated in cancers derived from multiple organs: A single-institutional methylome analysis using 1007 tissue specimens.2017

    • Author(s)
      Ohara K, Arai E*, Takahashi Y, Ito N, Shibuya A, Tsuta K, Kushima R, Tsuda H, Ojima H, Fujimoto H, Watanabe S, Katai H, Kinoshita T, Shibata T, Kohno T, Kanai Y.
    • Journal Title

      Carcinogenesis

      Volume: 38 Pages: 241-251

    • DOI

      10.1093/carcin/bgw209

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Genome-wide DNA methylation analysis during non-alcoholic steatohepatitis-related multistage hepatocarcinogenesis: comparison with hepatitis virus-related carcinogenesis.2017

    • Author(s)
      Kuramoto J, Arai E, Tian Y, Funahashi N, Hiramoto M, Nammo T, Nozaki Y, Takahashi Y, Ito N, Shibuya A, Ojima H, Sukeda A, Seki Y, Kasama K, Yasuda K, Kanai Y.
    • Journal Title

      Carcinogenesis.

      Volume: 38 Issue: 3 Pages: 261-270

    • DOI

      10.1093/carcin/bgx005

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cluster microRNAs miR-194 and miR-215 suppress the tumorigenicity of intestinal tumor organoids.2017

    • Author(s)
      Nakaoka T, Saito Y, Shimamoto Y, Muramatsu T, Kimura M, Kanai Y, Saito H.
    • Journal Title

      Cancer Sci,

      Volume: 108 Issue: 4 Pages: 678-684

    • DOI

      10.1111/cas.13165

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipidomic Signatures and Associated Transcriptomic Profiles of Clear Cell Renal Cell Carcinoma.2016

    • Author(s)
      Saito K, Arai E, Maekawa K, Ishikawa M, Fujimoto H, Taguchi R, Matsumoto K, Kanai Y, Saito Y.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 28932-28932

    • DOI

      10.1038/srep28932

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Genome-wide DNA methylation analysis during non-alcoholic steatohepatitis-related hepatocarcinogenesis2019

    • Author(s)
      Ying Tian, Eri Arai, Junko Kuramoto, Satomi Makiuchi, Noboru Tsuda, Hidenori Ojima, Yukihiro Fukamachi, Yoriko Takahashi, Nobuyoshi Hiraoka, Teruhiko Yoshida, Yae Kanai
    • Organizer
      11th American Association for Cancer Research-Japanese Cancer Association Joint Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 前がん段階から肝細胞がんに至るDNAメチル化異常2018

    • Author(s)
      金井弥栄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 肝炎ウイルス感染・アルコール多飲・脂肪肝を伴わない肝発がんのエピゲノム異常2018

    • Author(s)
      牧内里美, 新井恵吏, 藏本純子, 田迎, 深町幸宏, 高橋順子, 平岡伸介, 吉田輝彦, 金井弥栄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ゲノム・エピゲノム統合解析による胃発がん分子機構の解明2018

    • Author(s)
      楊夢晗, 新井恵吏, 坂本裕美, 戸塚裕彦, 谷口浩和, 吉田輝彦, 金井弥栄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 病理組織検体のエピゲノム等オミックス解析研究が明らかにするがんの多様性2018

    • Author(s)
      金井弥栄
    • Organizer
      第37回消化器病態生理勉強会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 病理組織検体のオミックス解析に見るがんの多様性2018

    • Author(s)
      金井弥栄
    • Organizer
      第50回日本臨床分子形態学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ゲノム研究・診療のための病理組織検体の取扱い―日本病理学会規程に基づいて2018

    • Author(s)
      金井弥栄
    • Organizer
      第32回関東臨床細胞学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒト多段階発がんのエピゲノム機構に関する分子病理学的研究2018

    • Author(s)
      金井弥栄
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 組織学的に特記すべき所見を示さない肝に発生する病因不明の肝細胞がんのエピゲノム異常2018

    • Author(s)
      牧内里美, 新井恵吏, 藏本純子, 田迎, 深町幸宏, 高橋順子, 平岡伸介, 吉田輝彦, 金井弥栄
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 若年性子宮体がんのゲノム網羅的DNAメチル化プロファイル2018

    • Author(s)
      真壁健, 新井恵吏, 平沢晃, 山上 亘, 進伸幸, 青木大輔, 金井弥栄
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ゲノム医療における病理組織検体取扱い2018

    • Author(s)
      金井弥栄
    • Organizer
      第3回日本肉腫学会・日本臨床肉腫学会合同年次総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Genome-wide DNA methylation analysis during nonalcoholic steatohepatitis-related multistage hepatocarcinogenesis: Comparison with hepatitis virus-related carcinogenesis2018

    • Author(s)
      Junko Kuramoto, Eri Arai, Ying Tian, Nobuaki Funahashi, Masaki Hiramoto, Takao Nammo, Yuichi Nozaki, Yoriko Takahashi, Nanako Ito, Ayako Shibuya, Hidenori Ojima, Aoi Sukeda, Yosuke Seki, Kazunori Kasama, Kazuki Yasuda, Yae Kanai
    • Organizer
      American Association for Cancer Research Annual Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] enome-wide DNA methylation analysis during nonalcoholic steatohepatitis-related multistage hepatocarcinogenesis: Comparison with hepatitis virus-related carcinogenesis,2018

    • Author(s)
      Kuramoto J, Arai E, Tian Y, Funahashi N, Hiramoto M, Nammo T, Nozaki Y, Takahashi Y, Ito N, Shibuya A, Ojima H, Sukeda A, Seki Y, Kasama K, Yasuda K, Kanai Y.
    • Organizer
      The 109th Annual Meeting of the American Association for Cancer Research
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] がん細胞の形態異常とゲノム・エピゲノム変化2017

    • Author(s)
      金井弥栄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Invited
  • [Presentation] 病理組織検体に見出されるDNAメチル化異常2017

    • Author(s)
      金井弥栄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Invited
  • [Presentation] 発がん過程におけるエピゲノム解析を中心とした多層オミックス統合解析2017

    • Author(s)
      金井弥栄
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] がんにおけるエピゲノム解析とその臨床展開2017

    • Author(s)
      金井弥栄
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 病理組織検体におけるエピゲノム等オミックス解析による個別化医療開発2017

    • Author(s)
      金井弥栄
    • Organizer
      生命化学系学会合同年会ConBio2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 個別化医療を目指したゲノム研究用病理組織検体取扱いの標準化2016

    • Author(s)
      金井弥栄
    • Organizer
      第 75 回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-10-08
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 肝発がんのエピゲノム機構2016

    • Author(s)
      金井弥栄
    • Organizer
      第57回日本臨床細胞学会総会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-05-29
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 肝発がん過程におけるエピゲノム解析2016

    • Author(s)
      金井弥栄
    • Organizer
      第12回肝免疫・ウイルス・フロンティア
    • Place of Presentation
      ソラシティカンファレンスセンター (東京都千代田区)
    • Year and Date
      2016-04-09
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Remarks] 慶應義塾大学医学部病理学教室・慶應義塾大学病院病理診断部・金井弥栄教授グループ

    • URL

      http://www.keio-pathology.net/kanai_group.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 慶應義塾大学医学部病理学教室・金井弥栄教授グループ

    • URL

      http://www.keio-pathology.net/kanai_group.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 慶應義塾大学医学部病理学教室金井弥栄教授グループ

    • URL

      http://keio-pathology.net/kanai_group.html

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 尿路上皮癌のリスク判定方法2019

    • Inventor(s)
      Kanai Yae, Arai Eri
    • Industrial Property Rights Holder
      Keio Univ, SEKISUI MEDICAL
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 尿路上皮癌のリスク判定方法2018

    • Inventor(s)
      金井弥栄・新井恵吏
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-051464
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] Method for assessing risk of hepatocellular carcinoma2018

    • Inventor(s)
      Kanai, Yae, et al.
    • Industrial Property Rights Holder
      Natl Cancer Ctr, SEKISUI MEDICAL
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 子宮体癌の予後の判定方法2018

    • Inventor(s)
      金井弥栄・新井恵吏・青木大輔・進伸幸・山上亘・真壁健
    • Industrial Property Rights Holder
      学校法人慶應義塾・積水メディカル株式会社
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-228276
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 尿路上皮癌のリスクの判定方法2018

    • Inventor(s)
      金井弥栄, 新井恵吏
    • Industrial Property Rights Holder
      金井弥栄, 新井恵吏
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-051464
    • Filing Date
      2018
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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