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Comprehensive analysis of LINE-1 hypomethylation level aimed at the development of new treatments for esophageal cancer

Research Project

Project/Area Number 23689061
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionKumamoto University

Principal Investigator

BABA Yoshifumi  熊本大学, 大学院生命科学研究部, 講師 (20599708)

Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥26,130,000 (Direct Cost: ¥20,100,000、Indirect Cost: ¥6,030,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2011: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
KeywordsLINE-1 / メチル化 / 予後因子 / エピジェネティクス / 食道癌 / Pyrosequence / pyrosequence
Research Abstract

Using more than 200 ESCC specimens,we quantified the LINE-1 methylation by utilizing the bisulfite pyrosequencing technology. LINE-1 hypomethylation in ESCC is associated with a shorter survival, thus suggesting that it has potential for use as a prognostic biomarker. Result of CGH array, LINE-1-hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6. In our cohort of 129 patients with ESCC, cases with CDK6-positive expression experienced worse clinical outcome compared with those with CDK6-negative expression, supporting the oncogenic role of CDK6 in ESCC. In addition, we found that the prognostic impact of LINE-1 hypomethylation might be attenuated by CDK6 expression. LINE-1 hypomethylation in ESCC might contribute to the acquisition of aggressive tumor behavior through genomic gains of oncogenes such as CDK6.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (20 results)

All 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (11 results)

  • [Journal Article] LINE-1 hypomethylation, DNA copy number alterations, and CDK6 amplification in esophageal squamous cell carcinoma2014

    • Author(s)
      Y. Baba, M. Watanabe, A. Murata, H. Shigaki, K. Miyake, T. Ishimoto, M. Iwatsuki, S. Iwagami, N. Yoshida, E. Oki, K. Sakamaki, M. Nakao, and H. Baba.
    • Journal Title

      Clin Cancer Res.

      Volume: 20 Issue: 5 Pages: 1114-1124

    • DOI

      10.1158/1078-0432.ccr-13-1645

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical implications of the LINE-1 methylation levels in patients with gastrointestinal cancer.2014

    • Author(s)
      Baba Y, Murata A, Watanabe M, Baba H.
    • Journal Title

      Surg Today

      Volume: In press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical implications of the LINE-1 methylation levels in patients with gastrointestinal cancer2013

    • Author(s)
      Baba Y, Murata A, Watanabe M, Baba H
    • Journal Title

      Surg Today

      Volume: (Epub ahead of print) Issue: 10 Pages: 1807-1816

    • DOI

      10.1007/s00595-013-0763-6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant methylation of LINE-1, SLIT2, MAL, and IGFBP7 in non-small cell lung cancer2013

    • Author(s)
      Suzuki M, Shiraishi K, Eguchi A, Ikeda K, Mori T, Yoshimoto K, Ohba Y, Ito Yamada T, Ito T, Baba Y, Baba H
    • Journal Title

      Oncol Rep

      Volume: 29(4) Issue: 4 Pages: 1308-14

    • DOI

      10.3892/or.2013.2266

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LINE-1 hypomethylation is associated with a poor prognosis among patients with curatively resected esophageal squamous cell carcinoma2013

    • Author(s)
      Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, Iwatsuki M, Sakamaki K, Ohashi Y, Baba H
    • Journal Title

      Ann Surg

      Volume: 257(3) Issue: 3 Pages: 449-55

    • DOI

      10.1097/sla.0b013e31826d8602

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis.2013

    • Author(s)
      Shigaki H, Baba Y, et al.
    • Journal Title

      Gastric Cancer

      Volume: in press Issue: 4 Pages: 480-487

    • DOI

      10.1007/s10120-012-0209-7

    • NAID

      40019845213

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LINE-1 hypomethylation in noncancerous esophageal mucosae is associated with smoking history2012

    • Author(s)
      Shigaki H, Baba Y, Watanabe M, Iwagami S, Miyake K, Ishimoto T, Iwatsuki M, Baba H
    • Journal Title

      Ann Surg Oncol

      Volume: 19(13) Issue: 13 Pages: 4238-43

    • DOI

      10.1245/s10434-012-2488-y

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma2012

    • Author(s)
      Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ida S, Nagai Y, Ishimoto T, Iwatsuki M, Sakamoto Y, Miyamoto Y, Baba H.
    • Journal Title

      Ann Surg Oncol

      Volume: 19(8) Issue: 8 Pages: 2726-32

    • DOI

      10.1245/s10434-011-2176-3

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LINE-1 Hypomethylation is Associated with a Poor Prognosis Among Patients with Curatively Resected Esophageal Squamous Cell Carcinoma2012

    • Author(s)
      Iwagami S, Baba Y, et al
    • Journal Title

      Ann Surg

      Volume: (印刷中)(In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 同時性・異時性頭頚部癌を有する食道癌症例におけるLINE-1メチル化レベル2013

    • Author(s)
      馬場祥史、渡邊雅之、吉田直矢、小澄敬祐、原田和人、村田飛鳥、岩上志朗、辛島龍一、石本崇胤、馬場秀夫
    • Organizer
      第65回日本気管食道学会総会ならびに学術講演会
    • Place of Presentation
      品川プリンスホテル(東京都)
    • Year and Date
      2013-11-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 食道扁平上皮癌におけるLINE-1低メチル化とDNAコピー数異常、CDK6増幅の関係2013

    • Author(s)
      馬場祥史、渡邊雅之、村田飛鳥、志垣博信、三宅慧輔、石本崇胤、岩槻政晃、岩上志朗、吉田直矢、馬場秀夫
    • Organizer
      第72回日本癌学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2013-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 食道癌におけるLINE-1メチル化レベルとDNAコピー数異常の関係2013

    • Author(s)
      馬場祥史、渡邊雅之、村田飛鳥、志垣博信、岩上志朗、石本崇胤、岩槻政晃、吉田直矢、馬場秀夫
    • Organizer
      第24回日本消火器癌発生学会
    • Place of Presentation
      石河県立音楽堂
    • Year and Date
      2013-09-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Pyrosequence technologyを用いた食道癌のエピゲノム解析2013

    • Author(s)
      馬場祥史、渡邊雅之、村田飛鳥、志垣博信、岩上志朗、石本崇胤、岩槻政晃、吉田直矢、馬場秀夫
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      マリンメッセ福岡
    • Year and Date
      2013-04-12
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Relationship between LINE-1 methylation level, allelic imbalance and PIK3CA mutation in esophageal squamous cell carcinoma2013

    • Author(s)
      Baba Y, Watanabe M, Murata A, Shigaki H, Iwagami S, Iwatsuki M, Ishimoto T, Baba H
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Walter E. Washington Convention Center(アメリカ・ワシントン)
    • Year and Date
      2013-04-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Prognostic significance of LINE-1 methylation level in esophageal squamous cell carcinoma2012

    • Author(s)
      馬場祥史
    • Organizer
      ASCO GI
    • Place of Presentation
      Moscone West Building(アメリカ・サンフランシスコ)
    • Year and Date
      2012-01-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Prognostic significance of LINE-1 methylation level in esophageal squamous cell carcinoma2012

    • Author(s)
      馬場祥史
    • Organizer
      ASCO GI
    • Place of Presentation
      アメリカ合衆国サンフランシスコMoscone West Building
    • Year and Date
      2012-01-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] Prognostic significance of LINE-1 methylation level2012

    • Author(s)
      馬場 祥史
    • Organizer
      ASCO2012 (poster discussion)
    • Place of Presentation
      Mc Cormick Place(アメリカ・シカゴ)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 食道癌におけるLINE-1メチル化レベル-Prognosis and Epigenetic Field Defect-2012

    • Author(s)
      馬場 祥史
    • Organizer
      第66回日本食道学会学術集会
    • Place of Presentation
      軽井沢プリンスホテルウエスト
    • Related Report
      2012 Annual Research Report
  • [Presentation] 上部消化管癌におけるLINE-1メチル化レベルのprognostic markerとしての意義2012

    • Author(s)
      馬場 祥史
    • Organizer
      第67回日本消化器外科学会
    • Place of Presentation
      富山県民会館
    • Related Report
      2012 Annual Research Report
  • [Presentation] 上部消化管癌におけるLINE-1メチル化レベルと予後の関係2012

    • Author(s)
      馬場 祥史
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市教育文化会館
    • Related Report
      2012 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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