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Epigenetic profiling of cfDNA in breast cancer samples

Research Project

Project/Area Number 16H05400
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research Institution株式会社関西メディカルネット(関西電力医学研究所) (2018)
Kyoto University (2016-2017)

Principal Investigator

SATO FUMIAKI  株式会社関西メディカルネット(関西電力医学研究所), 外科(神経内分泌腫瘍・乳癌)研究部, 上級特別研究員 (20467426)

Co-Investigator(Kenkyū-buntansha) 鈴木 栄治  京都大学, 医学研究科, 准教授 (00612897)
戸井 雅和  京都大学, 医学研究科, 教授 (10207516)
松村 謙臣  京都大学, 医学研究科, 准教授 (20452336)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords乳癌 / cfDNA / エピジェネティックス / 由来 / 乳がん / エピジェネティクス / 血中浮遊DNA / エピジェネティック / リキッドバイオプシー / 血中循環DNA / エピゲノム
Outline of Final Research Achievements

The aim of this study is to profile the origin of cfDNA epigenetically and to utilize the profile for cancer diagnosis and therapeutic response prediction. The epigenetic markers for the profiling were identified from comprehensive epigenetic array data, and primer-probe sets were established for digital PCR machine. To detect breast cancer-origin cfDNA, primer probe sets specific to hot spot mutations in PIK3CA and ESR1 were made. To identify epigenetic markers for each cell type was difficult, and combination of markers for different germ-layer cells will be necessary

Academic Significance and Societal Importance of the Research Achievements

癌症例のcfDNAの由来が判明することで、腫瘍組織内構成細胞のターンオーバーを推測することができると思われる。特に免疫細胞由来DNAの割合は腫瘍組織内の免疫活動の状況を反映していると考えられる。抗がん剤や抗体医薬で腫瘍内浸潤リンパ球(TIL)に対する研究が近年盛んになっている。更に、抗PD-1抗体薬等の免疫チェックポイント阻害剤の臨床応用が始まっているが、その効果予測因子の探求が盛んに行われている。既存の抗がん剤・抗体医薬による薬物療法だけでなく、この新規の免疫チェックポイント阻害療法の効果予測に重要な情報を提供することで、癌薬物療法の個別最適化に大きく寄与する可能性がある

Report

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

    (22 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network.2018

    • Author(s)
      Kiso M, Tanaka S, Saji S, Toi M, Sato F
    • Journal Title

      International Journal of Cancer

      Volume: 143 Issue: 11 Pages: 2905-2918

    • DOI

      10.1002/ijc.31645

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-time navigation system for sentinel lymph node biopsy in breast cancer patients using projection mapping with indocyanine green fluorescence2018

    • Author(s)
      Takada Masahiro、Takeuchi Megumi、Suzuki Eiji、Sato Fumiaki、Matsumoto Yoshiaki、Torii Masae、Kawaguchi-Sakita Nobuko、Nishino Hiroto、Seo Satoru、Hatano Etsuro、Toi Masakazu
    • Journal Title

      Breast Cancer

      Volume: - Issue: 6 Pages: 650-655

    • DOI

      10.1007/s12282-018-0868-2

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sal-like 4 protein levels in breast cancer cells are post-translationally down-regulated by tripartite motif?containing 212018

    • Author(s)
      Itou Junji、Li Wenzhao、Ito Shinji、Tanaka Sunao、Matsumoto Yoshiaki、Sato Fumiaki、Toi Masakazu
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 17 Pages: 6556-6564

    • DOI

      10.1074/jbc.ra117.000245

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SALL4 - KHDRBS3 network enhances stemness by modulating CD44 splicing in basal-like breast cancer2018

    • Author(s)
      Matsumoto Yoshiaki、Itou Junji、Sato Fumiaki、Toi Masakazu
    • Journal Title

      Cancer Medicine

      Volume: 7 Issue: 2 Pages: 454-462

    • DOI

      10.1002/cam4.1296

    • NAID

      120006457107

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Sal-like 4 - integrin α6β1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells.2017

    • Author(s)
      Itou J, Tanaka S, Li W, Iida A, Sehara-Fujisawa A, Sato F, Toi M.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1864 Pages: 76-76

    • NAID

      120005860049

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 乳癌の浸潤と転移の分子機序2017

    • Author(s)
      佐藤史顕
    • Journal Title

      日本臨牀 増刊号 乳癌学

      Volume: 75 Pages: 149-149

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Circulating cell-free DNA-based epigenetic assay can detect early breast cancer.2016

    • Author(s)
      Uehiro N, Sato F, Pu F, Tanaka S, Kawashima M, Kawaguchi K, Sugimoto M, Saji S, Toi M.
    • Journal Title

      Breast Cancer Res

      Volume: 18 Issue: 1 Pages: 129-129

    • DOI

      10.1186/s13058-016-0788-z

    • NAID

      120005973397

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A homeobox protein, NKX6.1, up-regulates interleukin-6 expression for cell growth in basal-like breast cancer cells.2016

    • Author(s)
      Li W, Itou J, Tanaka S, Nishimura T, Sato F, Toi M
    • Journal Title

      Exp Cell Res

      Volume: 343 Issue: 2 Pages: 177-177

    • DOI

      10.1016/j.yexcr.2016.03.023

    • NAID

      120005753812

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network.2019

    • Author(s)
      Kiso M, Tanaka S, Saji S, Toi M, Sato F
    • Organizer
      米国癌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Inhibition of metastasis with a peptide having the conserved amino acid residue of integrin a6 in breast cancer cells2018

    • Author(s)
      Sunao Tanaka, Junji Itou, Noriko Senda, Fumiaki Sato, Masakazu Toi
    • Organizer
      日本癌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] VEGF/NRP1 シグナルは乳癌細胞におけるfilopodia形成とmigrationを促進する2018

    • Author(s)
      木曾末厘乃、田中直、戸井雅和、佐藤史顕
    • Organizer
      日本乳癌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 日本人乳癌患者におけるオランザピン(アプレピタント非併用)の化学療法誘発性悪心嘔吐抑制効果2017

    • Author(s)
      西村友美、石黒洋、眞鍋恵理子、河口浩介、木曾末厘乃、鳥井雅恵、松本純明、川口展子、高田正泰、竹内恵、 鈴木栄治、佐藤史顕、戸井雅和
    • Organizer
      第25回日本乳癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Basal-like 乳がん症例におけるシスプラチン含む術前化学療法 の予後への影響に関する後向き解析2017

    • Author(s)
      山口絢音、石黒洋、鳥井雅恵、松本純明、川口展子、 高田正泰、鈴木栄治、竹内恵、佐藤史顕、戸井雅和
    • Organizer
      第25回日本乳癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 乳癌における乳房切除術後胸壁・所属リンパ節再発に対する 放射線療法成績の遡及的検討2017

    • Author(s)
      平田希美子、小野幸果、戸井雅和、佐藤史顕、鈴木栄治、竹内恵、高田正泰、吉村通央
    • Organizer
      第25回日本乳癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Basal-like 乳癌におけるSALL4-インテグリン系による移動能促進 機構の解明2017

    • Author(s)
      伊東潤二、田中直、佐藤史顕、戸井雅和
    • Organizer
      第75回日本癌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The mechanism of integrin alpha 6 activation on metastasis in basal-like breast cancer2017

    • Author(s)
      田中直、伊東潤二、佐藤史顕、戸井雅和
    • Organizer
      第75回日本癌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] VEGFA/NRP1 signal contributes to filopodia formation in breast cancer cells.2017

    • Author(s)
      Marina Kiso, Sunao Tanaka, Masakazu Toi, Fumiaki Sato.
    • Organizer
      AACR 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Basal-like乳癌細胞の転移におけるインテグリンα6の活性機構2016

    • Author(s)
      田中直、伊東潤二、佐藤史顕、戸井雅和
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Sal-like 4 (SALL4) promotes cell migration through up-regulation of integrin genes in basal-like breast cancer cells2016

    • Author(s)
      伊東潤二、田中直、佐藤史顕、戸井雅和
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Circulating DNAに対する12エピジェネティクマーカーパネルを用いた早期乳癌診断2016

    • Author(s)
      植弘奈津恵、佐藤史顕、佐治重衡、戸井雅和
    • Organizer
      日本乳癌学会
    • Place of Presentation
      東京ビックサイト
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Twelve epigenetic marker panel for circulating DNA in plasma can detect early breast cancer.2016

    • Author(s)
      Uehiro N, Sato F, Saji S, Toi M.
    • Organizer
      米国癌学会
    • Place of Presentation
      New Orleans
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] VEGFA/NRP1 signal contributes to cell adhesion and motility in breast cancer cells.2016

    • Author(s)
      Kiso M, Sato F, Sunao Tanaka, Masakazu Toi
    • Organizer
      米国癌学会
    • Place of Presentation
      New Orleans
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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

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