The significance of host immune status and microRNA abnormalities in EBV-associated tumor

• Project/Area Number: 17K08716
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: The University of Tokyo
• Principal Investigator: Shinozaki-Ushiku Aya 東京大学, 医学部附属病院, 講師 (60581824)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: EBウイルス / microRNA / 潜伏感染遺伝子 / Micro RNA / MicroRNA / マイクロRNA / 宿主免疫

Outline of Final Research Achievements

To explore the significance of immune host status during EBV-associated oncogenesis, analyses of EBV-microRNAs expression, latent gene expression and EBV copy number were performed using 90 cases of EBV-related tumors. EBV-microRNA expression and copy numbers were high in the relatively immunocompetent hosts. In addition, EBV-microRNA expression was higher in lymphoproliferative disorders than in monomorphic malignant lymphomas, suggesting the significance of EBV-microRNA in early stage of oncogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究ではEBVに関連した上皮性あるいはリンパ球性の腫瘍発生の過程において，比較的早期の段階からEBV由来のmicroRNAの発現が重要であることを明らかにした．高齢化や移植医療の発達などにより，潜在的な免疫不全状態の患者が増加し，これに伴ってEBVに関連した腫瘍発生が増加することが予想される．本研究がEBVに関連した腫瘍発生の機序の一端を明らかにすることにより，診断や治療における有益な情報となる可能性がある．

Research Products

• [Journal Article] Extranodal NK/T-cell lymphoma of the nasal cavity developed in a patient with intestinal Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorder. (2018)
  • Author(s): Furuya G, Abe H, Shinozaki-Ushiku A, Yamashita A, Ihara S, Hirata Y, Chiba A, Fujioka Y, Kurokawa M, Koike K, Fukayama M.
  • Journal Title: Pathol Res Pract Volume: 214 Issue: 7 Pages: 1051-1055
  • DOI: 10.1016/j.prp.2018.05.022
  • Peer Reviewed
• [Journal Article] CD47 expression in Epstein-Barr virus-associated gastric carcinoma: coexistence with tumor immunity lowering the ratio of CD8+/Foxp3+ T cells (2018)
  • Author(s): Abe Hiroyuki、Saito Ruri、Ichimura Takashi、Iwasaki Akiko、Yamazawa Sho、Shinozaki-Ushiku Aya、Morikawa Teppei、Ushiku Tetsuo、Yamashita Hiroharu、Seto Yasuyuki、Fukayama Masashi
  • Journal Title: Virchows archiv Volume: 印刷中 Issue: 4 Pages: 643-651
  • DOI: 10.1007/s00428-018-2332-2
  • Peer Reviewed
• [Journal Article] Clinical features and outcomes of secondary intraocular lymphoma (2017)
  • Author(s): Karakawa Ayako、Taoka Kazuki、Kaburaki Toshikatsu、Tanaka Rie、Shinozaki-Ushiku Aya、Hayashi Hiroyuki、Miyagi-Maeshima Akiko、Nishimura Yu、Uekusa Toshimasa、Kojima Yui、Fukayama Masashi、Kurokawa Mineo、Aihara Makoto
  • Journal Title: British Journal of Haematology Volume: - Issue: 4 Pages: 668-671
  • DOI: 10.1111/bjh.15005
  • Peer Reviewed
• [Journal Article] Polymorphic lymphoproliferative disorders in patients with rheumatoid arthritis are associated with a better clinical outcome (2017)
  • Author(s): Tsukui Daisuke、Kanda Hiroko、Shinozaki-Ushiku Aya、Tateishi Shoko、Takeshima Yusuke、Nagafuchi Yasuo、Sasaki Oh、Iwasaki Yukiko、Harada Hiroaki、Shibuya Mihoko、Sumitomo Shuji、Shoda Hirofumi、Kubo Kanae、Fujio Keishi、Nakamura Fumihiko、Kurokawa Mineo、Fukayama Masashi、Yamamoto Kazuhiko
  • Journal Title: Modern Rheumatology Volume: 23 Issue: 4 Pages: 1-5
  • DOI: 10.1080/14397595.2017.1387223
  • Peer Reviewed
• [Journal Article] Mizuno H, Koya J, Fujioka Y, Ibaraki T, Nakamura F, Hayashi A, Shinozaki-Ushiku A, Akamatsu N, Hasegawa K, Kokudo N, Fukuyama M, Kurokawa M. (2017)
  • Author(s): Extranodal NK/T cell lymphoma in a living donor liver transplant recipient.
  • Journal Title: Ann Hematol. Volume: Mar 9. Issue: 6 Pages: 1051-1052
  • DOI: 10.1007/s00277-017-2969-y
  • Peer Reviewed
• [Journal Article] EBウイルス関連胃癌 (2017)
  • Author(s): 牛久綾・牛久哲男
  • Journal Title: 消化器・肝臓内科 Volume: 2 Pages: 49-54
• [Journal Article] EBウイルス関連胃癌とH.pylori (2017)
  • Author(s): 牛久綾・牛久哲男
  • Journal Title: 臨床消化器内科 Volume: 32 Pages: 1497-1502
• [Presentation] EBV関連腫瘍における宿主の免疫状態およびmicroRNA異常の意義の解明 (2020)
  • Author(s): 久米 絢子, 牛久 綾, 牛久 哲男
  • Organizer: 第109回日本病理学会総会
• [Presentation] EBV関連腫瘍における宿主の免疫状態およびmicroRNA発現異常の意義の解明 (2019)
  • Author(s): 久米絢子, 牛久綾, 国田朱子, 深山正久, 牛久哲男
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] Epstein-Barr virus-associated gastric carcinoma -The roles of cellular and viral microRNAs in its carcinogenesis- (2017)
  • Author(s): Aya Shinozaki-Ushiku
  • Organizer: Belfast Pathology 2017 (10th Joint Meeting of the British Division of the International Academy of Pathology and the Pathologocal Society of Great Britaion & Ireland)
  • Int'l Joint Research
• [Remarks] 東京大学医学部 人体病理学・病理診断学ホームページ
  • URL: http://pathol.umin.ac.jp/
• [Remarks] 東京大学医学部 人体病理学・病理診断学分野のホームページ
  • URL: http://pathol.umin.ac.jp/