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5-hydroxymethylcytosine and clinicopathological features in ovarian serous carcinoma

Research Project

Project/Area Number 20K09646
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionKyushu University

Principal Investigator

Onoyama Ichiro  九州大学, 大学病院, 助教 (00444802)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsDNA脱メチル化 / 5hmC / 卵巣癌 / エピゲノム / 卵巣漿液性癌
Outline of Research at the Start

癌におけるエピジェネティクス研究はDNAメチル化とヒストン修飾を中心に大いに
発展してきたが、DNAメチル化が精力的に研究されて来たのに対して、DNA脱メチル化に関してはまだまだ解明されていないことが多い。申請者は最近、卵巣漿液性癌の転移症例で5hmCレベルが高いことを見出した。
そこで本研究では卵巣漿液性癌における5hmCレベルの違いが転移の有無とどのように関
わっているのかを明らかにすることを目的に解析を行う。5hmCと癌の進展・転移との関係およびその機構を明らかにすることは癌を全く新しい視点で捉える研究に繋がり、癌研究における新しい領域となることが期待できる。

Outline of Final Research Achievements

This project revealed that ovarian cancer cells showed higher levels of 5hmC compared with epithelial cells of normal ovary and fallopian tube. Notably, high-grade serous carcinomas (HGSCs) with lymph-node (LN) metastasis showed significantly higher levels of 5hmC compared with those without LN metastasis. Genome-wide 5hmC sequencing showed 5hmCs were adjacent to various oncogenes in HGSC cases regardless of LN metastasis, however, comparative gene ontology analysis revealed some characteristic pathways specific to HGSCs with LN metastasis.
These data indicated that epigenetic changes of 5hmC levels and their distributions could be implicated in LN metastasis in ovarian HGSCs.

Academic Significance and Societal Importance of the Research Achievements

5hmCとがんとの関係について着目した研究はこれまでにいくつかあるが、ほとんどの場合、臨床検体を用いた免疫染色で「がん細胞における5hmCレベルは低い」と結論づけているものであり、詳細な検討はなされていない。
今回、5hmCレベルとがんの進展・転移との関係の一端を明らかにすることができ、この研究を発展させることは全く新しい視点でがんを捉える研究に繋がると期待される。また、ゲノムにおける5hmCのdistributionの変化と臨床的特徴との関連を明らかにすることができれば、将来的にがんの診断・治療に応用できる研究となり、基礎研究、臨床研究の両面で価値が高くなる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (12 results)

All 2023 2022 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (6 results) Book (1 results)

  • [Journal Article] Secondary Adrenal Insufficiency Due to Isolated ACTH Deficiency Induced by Pembrolizumab: A Report of Two Cases of Uterine Endometrial Cancer2023

    • Author(s)
      Ichiro Onoyama, Minoru Kawakami, Kazuhisa Hachisuga, Shoji Maenohara, Keisuke Kodama, Hiroshi Yagi, Masafumi Yasunaga, Tatsuhiro Ohgami, Kazuo Asanoma, Hideaki Yahata, Yuya Kitamura, Ryuichi Sakamoto, Daisuke Kiyozawa and Kiyoko Kato
    • Journal Title

      Reports

      Volume: -

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer2021

    • Author(s)
      Suzuki I, Yoshida S, Tabu K, Kusunoki S, Matsumura Y, Izumi H, Asanoma K, Yagi H, Onoyama I, Sonoda K, Kohno K, Taga T, Itakura A, Takeda S, Kato K
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 4220-4220

    • DOI

      10.1038/s41598-021-83200-5

    • NAID

      120007044568

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fibronectin mediates activation of stromal fibroblasts by SPARC in endometrial cancer cells2021

    • Author(s)
      Yoshida Sachiko、Asanoma Kazuo、Yagi Hiroshi、Onoyama Ichiro、Hori Emiko、Matsumura Yumiko、Okugawa Kaoru、Yahata Hideaki、Kato Kiyoko
    • Journal Title

      BMC Cancer

      Volume: 21 Issue: 1 Pages: 1-12

    • DOI

      10.1186/s12885-021-07875-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Downregulation of 5-hydroxymethylcytosine is associated with the progression of cervical intraepithelial neoplasia2020

    • Author(s)
      Kato Masaya、Onoyama Ichiro、Kawakami Minoru、Yoshida Sachiko、Kawamura Keiko、Kodama Keisuke、Hori Emiko、Cui Lin、Matsumura Yumiko、Yagi Hiroshi、Asanoma Kazuo、Yahata Hideaki、Itakura Atsuo、Takeda Satoru、Kato Kiyoko
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 11 Pages: 0241482-0241482

    • DOI

      10.1371/journal.pone.0241482

    • NAID

      120007044541

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of Fbxw7 impairs development of and induces heterogeneous tumor formation in the mouse mammary gland2020

    • Author(s)
      Onoyama Ichiro、Nakayama Shogo、Shimizu Hideyuki、Nakayama Keiichi I.
    • Journal Title

      Cancer Research

      Volume: 80 Issue: 24 Pages: 5515-5530

    • DOI

      10.1158/0008-5472.can-20-0271

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 子宮体癌に対するペンブロリズマブ治療中にACTH欠損症を起こした2例2022

    • Author(s)
      小野山 一郎、川上 穣、蜂須賀 一寿、前之原 章司、小玉 敬亮、八木 裕史、安永 昌史、大神 達寛、奥川 馨、淺野間 和夫、矢幡 秀昭、北村 雄哉、坂本 竜一、加藤 聖子
    • Organizer
      第60回日本癌治療学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Epigenetic characterization of ovarian serous carcinoma with lymph-node metastasis by 5-hydroxymethylcytosine sequencing2022

    • Author(s)
      Ichiro Onoyama, Masaya Kato, Minoru Kawakami, Shoji Maenohara, Keisuke Kodama, Hiroshi Yagi, Kazuo Asanoma, Kiyoko Kato
    • Organizer
      第81回日本癌学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 5-hydroxymethylcytosine sequencing revealed epigenetic characteristics in ovarian serous carcinoma with lymph-node metastasis.2022

    • Author(s)
      Ichiro Onoyama, Masaya Kato, Minoru Kawakami, Kazuhisa Hachisuga, Nobuko Yasutake, Keisuke Kodama, Hiroshi Yagi, Tatsuhiro Ohgami, Masafumi Yasunaga, Kaoru Okugawa, Kazuo Asanoma, Hideaki Yahata, Emiko Hori, Kiyoko Kato
    • Organizer
      第64回日本婦人科腫瘍学会学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Downregulation of 5-hydroxymethylcytosine is associated with the progression of cervical intraepithelial neoplasia2021

    • Author(s)
      Ichiro Onoyama, Masaya Kato, Minoru Kawakami, Keiko Kawamura, Hiroshi Yagi , Kazuo Asanoma, Kiyoko Kato
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 5-ヒドロキシメチルシトシン量の低下は子宮頸部上皮内癌の進展に関係する2021

    • Author(s)
      川上穣、小野山一郎、加藤雅也、友延寛、安武伸子、吉田祥子、小玉敬亮、八木裕史、安永昌史、大神達寛、奥川馨、矢幡秀昭、加藤聖子
    • Organizer
      第63回日本婦人科腫瘍学会学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] Downregulation of 5-hydroxymethylcytosine is associated with the progression of cervical intraepithelial neoplasia2021

    • Author(s)
      Ichiro Onoyama, Masaya Kato, Minoru Kawakami, Sachiko Yoshida, Keiko Kawamura, Hiroshi Yagi , Kazuo Asanoma, Hideaki Yahata, Kiyoko Kato
    • Organizer
      第73回日本産科婦人科学会学術講演会
    • Related Report
      2020 Research-status Report
  • [Book] 子宮肉腫研究の最前線2023

    • Author(s)
      小野山一郎、加藤聖子
    • Total Pages
      6
    • Publisher
      診断と治療社
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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