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Role of circulating MYCN in recurrence and/or metastasis of hepatocellular carcinoma as a biomarker and/or regulator

Research Project

Project/Area Number 18K15833
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

QIN Xian-Yang  国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (60756815)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsMYCN / 肝がん / バイオマーカー / 代謝 / 脂質 / がん幹細胞 / オミクス解析 / エクソソーム / 予後予測 / liquid biopsy
Outline of Final Research Achievements

Previous genome-wide transcriptome screen identified that MYCN expression marked an EpCAM+ cancer stem cell (CSC)-like subpopulation and was a candidate therapeutic target for the prevention of hepatocellular carcinoma (HCC). By the combination of LC-TOFMS-based metabolome analysis and RNA-seq-based transcriptome analysis, I found that the content of unsaturated fatty acids was increased in MYCN high expression CSC-like HCC cells and inhibition of lipid desaturation suppressed MYCN gene expression and cell/sphere proliferation of HCC cells. In addition, I succeeded in quantitatively measuring MYCN protein levels in both human serum and the isolated exosome samples. I found that serum protein levels of MYCN expression were significantly higher in HCC patients than that in healthy controls, and were significantly decreased after surgical resection of tumors. These findings suggested MYCN might server as a therapeutic target and novel biomarker for HCC.

Academic Significance and Societal Importance of the Research Achievements

医療技術の進歩により、がん全体の死亡率が低下しつつある中、肝がんは逆に死亡率が増加しているがんの1つである。日本において、肝がんの年間罹患数が約40,000人であるのに対し、年度死亡数は約30,000人であり、極めて死亡率の高いがんである(Hori et al. Jpn J Clin Oncol 2015)。本研究の成果とした血中MYCNを指標とした肝がんの診断や予後・薬効予測バイオマーカーを活用し、患者さんの予後の改善につながることを願っている。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018 Other

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (8 results) (of which Int'l Joint Research: 2 results) Remarks (2 results)

  • [Journal Article] Imaging of the ex vivo transglutaminase activity in liver macrophages of sepsis mice2020

    • Author(s)
      Su Ting、Qin Xian-Yang、Furutani Yutaka、Yu Wenkui、Kojima Soichi
    • Journal Title

      Analytical Biochemistry

      Volume: 597 Pages: 113654-113654

    • DOI

      10.1016/j.ab.2020.113654

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lipid desaturation-associated endoplasmic reticulum stress regulates MYCN gene expression in hepatocellular carcinoma cells2020

    • Author(s)
      Qin Xian-Yang、Su Ting、Yu Wenkui、Kojima Soichi
    • Journal Title

      Cell Death & Disease

      Volume: 11(1) Issue: 1 Pages: 66-66

    • DOI

      10.1038/s41419-020-2257-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MicroRNA‐493‐5p‐mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion2020

    • Author(s)
      Yasukawa Ken、Liew Lee Chuen、Hagiwara Keitaro、Hironaka‐Mitsuhashi Ai、Qin Xian‐Yang、Furutani Yutaka、Tanaka Yasuhito、Nakagama Hitoshi、Kojima Soichi、Kato Takashi、Ochiya Takahiro、Gailhouste Luc
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 3 Pages: 869-880

    • DOI

      10.1111/cas.14292

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevention of arachidonic acid?induced liver injury by controlling oxidative stress?mediated transglutaminase activation with garlic extracts2019

    • Author(s)
      Qin Xian-Yang、Su Ting、Kojima Soichi
    • Journal Title

      Experimental and Therapeutic Medicine

      Volume: 19(2) Pages: 1522-1527

    • DOI

      10.3892/etm.2019.8384

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-interleukin-6 receptor antibody treatment ameliorates postoperative adhesion formation2019

    • Author(s)
      Naoki Uyama, Hiroko Tsutsui, Songtao Wu, Koubun Yasuda, Etsuro Hatano, Xian-Yang Qin, Soichi Kojima, Jiro Fujimoto
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 17558-17571

    • DOI

      10.1038/s41598-019-54175-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An interferon-like small chemical compound CDM-3008 suppresses hepatitis B virus through induction of interferon-stimulated genes2019

    • Author(s)
      Furutani Yutaka、Toguchi Mariko、Shiozaki-Sato Yumi、Qin Xian-Yang、Ebisui Etsuko、Higuchi Shoko、Sudoh Masayuki、Suzuki Harukazu、Takahashi Nobuaki、Watashi Koichi、Wakita Takaji、Kakeya Hideaki、Kojima Soichi
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 6 Pages: e0216139-e0216139

    • DOI

      10.1371/journal.pone.0216139

    • NAID

      120006644069

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of stearoyl-CoA desaturase-1 activity suppressed SREBP signaling in colon cancer cells and their spheroid growth.2019

    • Author(s)
      Qin, X-Y., and Kojima, S.
    • Journal Title

      Gastrointest. Disords.

      Volume: 1 Issue: 1 Pages: 191-200

    • DOI

      10.3390/gidisord1010014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid2018

    • Author(s)
      Qin XY, Suzuki H, Honda M, Okada H, Kaneko S, Inoue I, Ebisui E, Hashimoto K, Carninci P, Kanki K, Tatsukawa H, Ishibashi N, Masaki T, Matsuura T, Kagechika H, Toriguchi K, Hatano E, Shirakami Y, Shiota G, Shimizu M, Moriwaki H, Kojima S
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 115 Issue: 19 Pages: 4969-4974

    • DOI

      10.1073/pnas.1802279115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reply to Yoshida: Liver cancer stem cells: Identification and lipid metabolic reprogramming.2018

    • Author(s)
      Qin, X-Y., Dohmae, N., and Kojima, S.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 115 Issue: 28

    • DOI

      10.1073/pnas.1808740115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prevention of acute liver injury by suppressing plasma kallikrein-dependent activation of latent TGF-β.2018

    • Author(s)
      Li, M., Qin, X-Y., Furutani, Y., Inoue, I., Sekihara, S., Kagechika, H., and Kojima, S.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 504 Issue: 4 Pages: 857-864

    • DOI

      10.1016/j.bbrc.2018.09.026

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Arachidonic acid suppresses hepatic cell growth through oxidative stress-mediated activation of nuclear transglutaminase.2018

    • Author(s)
      Qin, X-Y., Lu, J., Cai, M., and Kojima, S.
    • Journal Title

      FEBS Open Bio

      Volume: 8 Issue: 10 Pages: 1703-1710

    • DOI

      10.1002/2211-5463.12511

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 細胞と組織レベルにおける肝脂質代謝解析による肝発癌への不飽和脂肪酸関与の検証2019

    • Author(s)
      秦 咸陽、小嶋 聡一
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 不飽和脂肪酸の代謝リプログラミングを標的とする肝がん幹細胞の増殖制御2019

    • Author(s)
      秦咸陽、小嶋聡一
    • Organizer
      第23回日本がん分子標的治療学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 非環式レチノイド及びビタミンK2誘導体によるトランスグルタミナーゼの立体構造変化の制御2019

    • Author(s)
      秦 咸陽,影近 弘之,小嶋 聡一
    • Organizer
      日本レチノイド研究会第30回学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identification of MYCN as a prognostic biomarker of liver cancer stem cells and therapeutic target for recurrence of hepatocellular carcinoma2019

    • Author(s)
      Xian-Yang Qin and Soichi Kojima
    • Organizer
      JDDW2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] レチノイドによるMYCN陽性肝癌幹細胞の選択排除2018

    • Author(s)
      秦咸陽、小嶋聡一
    • Organizer
      第22回日本がん分子標的治療学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Multi-omics analyses on the effect of acyclic retinoid in selective depletion of liver cancer stem cells2018

    • Author(s)
      Xian-Yang Qin, Soichi Kojima
    • Organizer
      THE FOURTH INTERNATIONAL FASEB CONFERENCE ON RETINOIDS
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肝発癌における不飽和脂肪酸の役割に関する検討2018

    • Author(s)
      秦咸陽、小嶋聡一
    • Organizer
      第25回肝細胞研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 非環式レチノイドによる肝癌幹細胞排除における不飽和脂肪酸の関与2018

    • Author(s)
      秦咸陽、小嶋聡一
    • Organizer
      日本レチノイド研究会第29回学術集会
    • Related Report
      2018 Research-status Report
  • [Remarks] http://www.riken.jp/pr/press/2018/20180424_1/

    • Related Report
      2018 Research-status Report
  • [Remarks] http://www.riken.jp/en/pr/press/2018/20180424_1/

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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