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Epigenome profiling of precancerous condition in hepatocarcinogenesis using purified human hepatocytes

Research Project

Project/Area Number 25460487
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionKeio University (2015)
National Cancer Center Japan (2013-2014)

Principal Investigator

Arai Eri  慶應義塾大学, 医学部, 講師 (40446547)

Co-Investigator(Renkei-kenkyūsha) GOTOH Masahiro  国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (00291138)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsエピゲノム / 純化細胞 / 前がん状態 / 肝細胞がん / 慢性肝炎 / 肝硬変 / 肝炎ウイルス / DNAメチル化 / ヒストン修飾 / ウイルス性肝炎 / アルコール性肝炎 / 非アルコール性脂肪肝
Outline of Final Research Achievements

Thirty-one samples of hepatocytes with precancerous and normal condition could be purified from partial hepatectomy specimens of patients with metastatic carcinoma and hepatocellular carcinoma associated with hepatitis B or C viral infection. Methylome analysis was performed using Infinium HumanMethylation450k BeadChip. The incidence of DNA methylation alterations was higher at the precancerous stage of HCV-positive patients than that of HBV-positive patients. Many Infinium probes showed HCV-positive-specific DNA methylation alterations throughout the genome, by contrast to HBV-positive patient-specific ones. Although DNA methylation profile of purified hepatocytes exhibited almost similar trend with liver tissue samples, some characteristic profiles appeared significant in purified cells. Cell purification from surgical specimen enabled histone modification profiling which is applicable to personal differentiation or clinical analysis.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (40 results)

All 2016 2015 2014 2013 Other

All Journal Article (16 results) (of which Peer Reviewed: 14 results,  Open Access: 9 results,  Acknowledgement Compliant: 5 results) Presentation (22 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)

  • [Journal Article] Epigenetic clustering of gastric carcinomas based on DNA methylation profiles at the precancerous stage: its correlation with tumor aggressiveness and patient outcome.2015

    • Author(s)
      Yamanoi K, Arai E, Tian Y, Takahashi Y, Miyata S, Sasaki H, Chiwaki F, Ichikawa H, Sakamoto H, Kushima R, Katai H, Yoshida T, Sakamoto M, Kanai Y.
    • Journal Title

      Carcinogenesis

      Volume: 36 Issue: 5 Pages: 509-520

    • DOI

      10.1093/carcin/bgv013

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas.2015

    • Author(s)
      Arai E, Gotoh M, Tian Y, Sakamoto H, Ono M, Matsuda A, Takahashi Y, Miyata S, Totsuka H, Chiku S, Komiyama M, Fujimoto H, Matsumoto K, Yamada T, Yoshida T, Kanai Y.
    • Journal Title

      Int J Cancer

      Volume: 137 Issue: 11 Pages: 2589-2606

    • DOI

      10.1002/ijc.29630

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Tumour multifocality and grade predict intravesical recurrence after nephroureterectomy in patients with upper urinary tract urothelial carcinoma without a history of bladder cancer.2015

    • Author(s)
      Narukawa T, Hara T, Arai E, Komiyama M, Kawahara T, Kanai Y, Fujimoto H.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 45 Issue: 5 Pages: 488-93

    • DOI

      10.1093/jjco/hyv019

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis.2014

    • Author(s)
      Takaki Y, Saito Y, Takasugi A, Toshimitsu K, Yamada S, Muramatsu T, Kimura M, Sugiyama K, Suzuki H, Arai E, Ojima H, Kanai Y, Saito H.
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 10 Pages: 1254-1260

    • DOI

      10.1111/cas.12498

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease.2014

    • Author(s)
      Sato T, Arai E, Kohno T, Takahashi Y, Miyata S, Tsuta K, Watanabe S, Soejima K, Betsuyaku T, Kanai Y.
    • Journal Title

      Int J Cancer

      Volume: 135 Pages: 319-34

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome2014

    • Author(s)
      Arai E, Sakamoto H, Ichikawa H, Totsuka H, Chiku S, Gotoh M, Mori T, Nakatani T, Ohnami S, Nakagawa T, Fujimoto H, Wang L, Aburatani H, Yoshida T, Kanai Y.
    • Journal Title

      Int J Cancer

      Volume: 135 Issue: 6 Pages: 1330

    • DOI

      10.1002/ijc.28768

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multilayer-omics analyses of human cancers: Exploration of biomarkers and drug targets based on the activities of the International Human Epigenome Consortium.2014

    • Author(s)
      Kanai Y, Arai E.
    • Journal Title

      Front Genetics

      Volume: 5 Pages: 24-24

    • DOI

      10.3389/fgene.2014.00024

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive exploration of novel chimeric transcripts in clear cell renal cell carcinomas using whole transcriptome analysis.2014

    • Author(s)
      Gotoh M, Ichikawa H, Arai E, Chiku S, Sakamoto H, Fujimoto H, Hiramoto M, Nammo T, Yasuda K, Yoshida T, Kanai Y.
    • Journal Title

      Genes Chromosomes Cancer

      Volume: 53 Issue: 12 Pages: 1018-1032

    • DOI

      10.1002/gcc.22211

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes.2014

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

      BMC Cancer

      Volume: 14 Issue: 1 Pages: 772-772

    • DOI

      10.1186/1471-2407-14-772

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 多層的オミックス解析に基づく診断薬・治療薬シーズ同定2014

    • Author(s)
      金井弥栄,新井恵吏
    • Journal Title

      病理と臨床

      Volume: 32 Pages: 830-8

    • Related Report
      2014 Research-status Report
  • [Journal Article] 国際ヒトエピゲノムコンソーシアム (IHEC)の展開.2014

    • Author(s)
      金井弥栄,新井恵吏
    • Journal Title

      実験医学

      Volume: 32 Pages: 3030-6

    • Related Report
      2014 Research-status Report
  • [Journal Article] Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: its correlation with smoking history and chronic obstructive pulmonary disease.2014

    • Author(s)
      Sato T, Arai E, Kohno T, Takahashi Y, Miyata S, Tsuta K, Watanabe S, Soejima K, Betsuyaku T, Kanai Y.
    • Journal Title

      Int J Cancer

      Volume: in press Issue: 2 Pages: 319-334

    • DOI

      10.1002/ijc.28684

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bile Acids Increase Levels of microRNAs 221 and 222, Leading to Degradation of CDX2 During Esophageal Carcinogenesis2013

    • Author(s)
      J. Matsuzaki, H. Suzuki, H. Tsugawa, M. Watanabe, S. Hossain, T. Akaike, T. Hibi, et. al.
    • Journal Title

      Gastroenterology

      Volume: (In Press) Issue: 6 Pages: 1300-1311

    • DOI

      10.1053/j.gastro.2013.08.008

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] DNA methylation profiles at precancerous stages associated with recurrence of lung adenocarcinoma.2013

    • Author(s)
      Sato T, Arai E, Kohno T, Tsuta K, Watanabe S, Soejima K, Betsuyaku T, Kanai Y.
    • Journal Title

      PLOS One

      Volume: 8(3) Issue: 3 Pages: e59444-e59444

    • DOI

      10.1371/journal.pone.0059444

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ability of preoperative 3.0-Tesla magnetic resonance imaging to predict the absence of side-specific extracapsular extension of prostate cancer2013

    • Author(s)
      Hara T, Nakanishi H, Nakagawa T, Komiyama M, Kawahara T, Manabe T, Miyake M, Arai E, Kanai Y, Fujimoto H
    • Journal Title

      Int J Urol

      Volume: 20 Issue: 10 Pages: 993

    • DOI

      10.1111/iju.12091

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic risk stratification of patients with urothelial carcinoma of the bladder with recurrence after radical cystectomy2013

    • Author(s)
      Nakagawa T, Hara T, Kawahara T, Ogata Y, Nakanishi H, Komiyama M, Arai E, Kanai Y, Fujimoto H
    • Journal Title

      J Urol

      Volume: 189 Issue: 4 Pages: 1275

    • DOI

      10.1016/j.juro.2012.10.065

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Epigenome landscape of human normal purified hepatocytes and genome-epigenome interaction: analysis by the International Human Epigenome Consortium (IHEC)2016

    • Author(s)
      Arai E, Miura F, Totoki Y, Yamashita S, Tian Y, Gotoh M, Ojima H, Nakamura H, Hama N, Kato M, Kimura H, Suzuki Y, Ito T, Shibata T, Kanai Y
    • Organizer
      Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics
    • Place of Presentation
      マウイ(米国)
    • Year and Date
      2016-02-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Reference epigenome mapping of hepatocytes: participation in International Human Epigenome Consortium (IHEC)2015

    • Author(s)
      Arai E, Miura F, Totoki Y, Yamashita S, Tian Y, Gotoh M, Ojima H, Nakamura H, Hama N, Suzuki Y, Ito T, Shibata T, Kanai Y
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Epigenome alterations in precancerous conditions associated with hepatitis virus infection2015

    • Author(s)
      新井恵吏、田迎、後藤政広、高橋順子、尾島英知、小菅智男、金井弥栄
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Genome-wide DNA methylation analysis in precancerous conditions associated with hepatitis B virus and hepatitis C virus infection2015

    • Author(s)
      Arai E, Tian Y, Gotoh M, Takahashi Y, Ojima H, Kosuge T, Kanai Y
    • Organizer
      American Association of Cancer Research Annual Meeting 2016
    • Place of Presentation
      フィラデルフィア(米国)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 逆行分析前方シミュレーションモデルを用いた腎細胞がんのバイオマーカーならびに治療標的分子の同定2014

    • Author(s)
      新井恵吏、高橋順子、坂本裕美、尾野雅哉、宮田彩香、藤元博行、山田哲司、吉田輝彦、金井弥栄
    • Organizer
      日本癌学会第73回学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 腎細胞がんに発現する新規融合遺伝子の同定2014

    • Author(s)
      後藤政広、市川仁、新井恵吏、知久季倫、坂本裕美、藤元博行、平本正樹、南茂隆生、安田和基、吉田輝彦、金井弥栄
    • Organizer
      日本癌学会第73回学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 非小細胞肺がんにおけるPTPRHのDNA低メチル化と予後への関与2014

    • Author(s)
      佐藤崇、副島研三、新井恵吏、浜本純子、安田浩之、荒井大輔、石岡宏太、扇野圭子、楢木克彦、河野隆志、渡辺俊一、金井弥栄、別役智子
    • Organizer
      日本癌学会第73回学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] CpGアイランドメチル化形質陽性腎淡明細胞がんの多層的オミックス解析2014

    • Author(s)
      新井恵吏、坂本裕美、尾野雅哉、高橋順子、宮田彩香、藤元博行、後藤政広、山田哲司、金井弥栄
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島市
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] CpGアイランドメチル化形質陽性腎細胞がんのDNAメチル化診断法の開発2014

    • Author(s)
      田迎、新井恵吏、後藤政広、藤元博行、金井弥栄
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島市
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 腎細胞がんに発現する新規融合遺伝子の同定2014

    • Author(s)
      後藤政広、市川仁、新井恵吏、知久季倫、坂本裕美、藤元博行、安田和基、吉田輝彦、金井弥栄
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島市
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 胃がん症例の非がん胃粘膜におけるDNAメチル化プロファイルが、がんの悪性度・症例の予後と相関する2014

    • Author(s)
      山ノ井一裕、新井恵吏、高橋順子、宮田彩香、九嶋亮治、片井均、坂元亨宇、金井弥栄
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島市
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Multilayer omics analyses in CpG island methylator phenotype clear cell renal cell carcinomas2014

    • Author(s)
      Arai E, Sakamoto H, Ono M, Takahashi Y, Miyata S, Fujimoto H, Gotoh M, Yamada T, Kanai Y.
    • Organizer
      American Association of Cancer Research 105th Annual Meeting 2014
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Epigenetic clustering of gastric carcinoma based on DNA methylation profiles at the precancerous stage: its correlation with tumor aggressiveness and patient outcome2014

    • Author(s)
      Yamanoi K, Arai E, Takahashi Y, Miyata S, Kushima R, Katai H, Sakamoto M, Kanai Y.
    • Organizer
      American Association of Cancer Research 105th Annual Meeting 2014
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Research-status Report
  • [Presentation] 腎細胞がんの多層的オミックス解析2013

    • Author(s)
      新井恵吏、坂本裕美、尾野雅哉、高橋順子、宮田彩香、藤元博行、後藤政広、山田哲司、吉田輝彦、金井弥栄
    • Organizer
      第7回日本エピジェネティクス研究会年会
    • Place of Presentation
      奈良
    • Related Report
      2013 Research-status Report
  • [Presentation] CpGアイランドメチル化形質陽性腎細胞がんのDNAメチル化診断法の開発2013

    • Author(s)
      田迎、新井恵吏、後藤政広、藤元博行、金井弥栄
    • Organizer
      第7回日本エピジェネティクス研究会年会
    • Place of Presentation
      奈良
    • Related Report
      2013 Research-status Report
  • [Presentation] 腎細胞癌の多層的オミックス解析2013

    • Author(s)
      新井恵吏、坂本裕美、尾野雅哉、高橋順子、宮田彩香、藤元博行、後藤政広、山田哲司、吉田輝彦、金井弥栄
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] CpGアイランドメチル化形質腎細胞がんの多層的オミックス解析2013

    • Author(s)
      新井恵吏、坂本裕美、尾野雅哉、高橋順子、宮田彩香、藤元博行、澁谷亜矢子、後藤政広、山田哲司、吉田輝彦、金井弥栄
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] CpGアイランドメチル化形質マーカー遺伝子のDNAメチル化レベルを指標とする腎細胞がんの予後診断法の開発2013

    • Author(s)
      田迎、新井恵吏、後藤政広、藤元博行、金井弥栄
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Multilayer-Omics (Whole-Exome, Methylome and Transcriptome) Analysis Identifies the Wnt/β-catenin Pathway as a Key Player in the Development of Renal Cell Carcinoma2013

    • Author(s)
      Arai E, Sakamoto H, Ichikawa H, Totsuka H, Gotoh M, Mori T, Ohnami S, Nakagawa T, Fujimoto H, Wang L, Aburatani H, Yoshida T, Kanai Y
    • Organizer
      103rd American Association of Cancer Research Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] DNA methylation profiles at precancerous stage cluster lung adenocarcinomas into sub clusters associated with carcinogenic pathway, clinicopathological aggressiveness and patient outcome.2013

    • Author(s)
      Sato T, Arai E, Kohno T, Tsuta K, Watanabe S, Soejima K, Betsuyaku T, Kanai Y
    • Organizer
      103rd American Association of Cancer Research Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Epigenetic clustering of gastric carcinoma based on DNA methylation profiles at the precancerous stage: its correlation with tumor aggressiveness and patient outcome2013

    • Author(s)
      Yamanoi K, Arai E, Takahashi Y, Miyata S, Kushima R, Katai H, Sakamoto M, Kanai Y
    • Organizer
      The 4th JCA-AACR Special Joint Conference
    • Place of Presentation
      Maihama, Urayasu-shi, Chiba
    • Related Report
      2013 Research-status Report
  • [Presentation] Epigenome mapping in purified human hepatocytes2013

    • Author(s)
      Arai E, Miura F, Yamashita S, Shibata T, Ito T, Suzuki Y, Tian Y, Gotoh M, Ojima H, Kosuge T, Kanai Y
    • Organizer
      IHEC Annual Meeting 2013, Berlin
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2013 Research-status Report
  • [Remarks] 国立がん研究センター研究所 分子病理分野 研究内容

    • URL

      http://www.ncc.go.jp/jp/nccri/divisions/01path/01path01.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 国立がん研究センター研究所 発がん機構研究グループ 分子病理分野

    • URL

      http://www.ncc.go.jp/jp/nccri/divisions/01path/index.html

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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