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A search for moleculary targets of gliomas based on transcriptome analysis

Research Project

Project/Area Number 16K10766
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Hayano Azusa  京都府立医科大学, 医学(系)研究科(研究院), 研究員 (10379018)

Co-Investigator(Kenkyū-buntansha) 池中 一裕  生理学研究所, 生体機能調節研究領域, 特別協力研究員 (00144527)
山中 龍也  京都府立医科大学, 医学部, 教授 (20323991)
川口 淳  佐賀大学, 医学部, 教授 (60389319)
Research Collaborator Takashima Yasuo  
Iwadate Yasuo  
Yoshida Kenichi  
Suzuki Takayoshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsglioma / RNA seuence / prognosis / molecular target / 神経膠腫 / トランスクリプトーム / 免疫関連遺伝子 / 高速シーケンサー / トランスクリプトーム解析 / 脳腫瘍 / 分子標的治療 / トランスレーショナルリサーチ / 脳神経疾患
Outline of Final Research Achievements

We analyzed RNA sequence data on several glioma tissues. We also conducted expression profiling of immuno-related gene using data of 158 glioblastoma multiforme (GBM) patients with clinical information available at The Cancer Genome Atlas. The results revealed that Th1HighTh2Low and Th1LowTh2Low statuses indicated better prognosis than Th1HighTh2High, and were evaluated based on the down regulation of PD-L1, PD-L2, and PD-1. These results suggest that low Th2 balance and low activity of the PD-L1/PD-1 axis predict good prognosis in GBM. Furthermore, CD276 expression and the gene signature composed of GATA3 and LGALS3 are effective for prognosis in GBM and will help us understanding target pathways for immunotherapy in GBM.

Academic Significance and Societal Importance of the Research Achievements

本研究は神経膠腫のトランスクリプトーム解析を基盤とした悪性神経膠腫の新たなるバイオマーカー, 分子標的創薬の展開を目指したトランスレーショナル研究である。本研究により悪性神経膠腫の診断学・治療学のbreak-throughをもたらす期待がある。

Report

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

    (34 results)

All 2019 2018 2017 2016 Other

All Journal Article (22 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 22 results,  Open Access: 8 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Book (3 results) Remarks (2 results)

  • [Journal Article] CD276 and the gene signature composed of GATA3 and LGALS3 enable prognosis prediction of glioblastoma multiforme2019

    • Author(s)
      Takashima Yasuo、Kawaguchi Atsushi、Hayano Azusa、Yamanaka Ryuya
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 5 Pages: e0216825-e0216825

    • DOI

      10.1371/journal.pone.0216825

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell-type specific sensitivity of bortezomib in the methotrexate-resistant primary central nervous system lymphoma cells2019

    • Author(s)
      Hayano Azusa、Takashima Yasuo、Yamanaka Ryuya
    • Journal Title

      International Journal of Clinical Oncology

      Volume: April Issue: 9 Pages: 1020-1029

    • DOI

      10.1007/s10147-019-01451-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma2019

    • Author(s)
      Takashima Yasuo、Kawaguchi Atsushi、Iwadate Yasuo、Hondoh Hiroaki、Fukai Junya、Kajiwara Koji、Hayano Azusa、Yamanaka Ryuya
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: e0210400-e0210400

    • DOI

      10.1371/journal.pone.0210400

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The expression of PD-1 ligands and IDO1 by macrophage/microglia in primary central nervous system lymphoma2018

    • Author(s)
      Miyasato Yuko、Takashima Yasuo、Takeya Hiroto、Yano Hiromu、Hayano Azusa、Nakagawa Takenobu、Makino Keishi、Takeya Motohiro、Yamanaka Ryuya、Komohara Yoshihiro
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 58 Issue: 2 Pages: 95-101

    • DOI

      10.3960/jslrt.18001

    • NAID

      130007403913

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Target amplicon exome-sequencing identifies promising diagnosis and prognostic markers involved in RTK-RAS and PI3K-AKT signaling as central oncopathways in primary central nervous system lymphoma2018

    • Author(s)
      Takashima Yasuo、Sasaki Yasushi、Hayano Azusa、Homma Jumpei、Fukai Junya、Iwadate Yasuo、Kajiwara Koji、Ishizawa Shin、Hondoh Hiroaki、Tokino Takashi、Yamanaka Ryuya
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 44 Pages: 27471-27486

    • DOI

      10.18632/oncotarget.25463

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correlation between lower balance of Th2 helper T-cells and expression of PD-L1/PD-1 axis genes enables prognostic prediction in patients with glioblastoma2018

    • Author(s)
      Takashima Yasuo、Kawaguchi Atsushi、Kanayama Tomohiko、Hayano Azusa、Yamanaka Ryuya
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 27 Pages: 19065-19078

    • DOI

      10.18632/oncotarget.24897

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Programmed Cell Death Ligand 1 Expression in Primary Central Nervous System Lymphomas: A Clinicopathological Study.2017

    • Author(s)
      Hayano A, Komohara Y, Takashima Y, Takeya H, Homma J, Fukai J, Iwadate Y, Kajiwara K, Ishizawa S, Hondoh H, Yamanaka R.
    • Journal Title

      Anticancer Research

      Volume: 37 Pages: 5655-5666

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects and safety of mechanical bathing as a complementary therapy for terminal stage cancer patients from the physiological and psychological perspective: a pilot study2017

    • Author(s)
      Fujimoto Sawako、Iwawaki Yoko、Takishita Yukie、Yamamoto Yoko、Murota Masako、Yoshioka Saori、Hayano Azusa、Hosokawa Toyoshi、Yamanaka Ryuya
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 47 Issue: 11 Pages: 1066-1072

    • DOI

      10.1093/jjco/hyx122

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Trilateral retinoblastoma: A systematic review of 211 cases2017

    • Author(s)
      Yamanaka Ryuya、Hayano Azusa、Takashima Yasuo
    • Journal Title

      Neurosurgical Review

      Volume: - Issue: 1 Pages: 39-48

    • DOI

      10.1007/s10143-017-0890-4

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Secondary Intracranial Tumors Following Radiotherapy for Pituitary Adenomas: A Systematic Review2017

    • Author(s)
      Yamanaka Ryuya、Abe Eisuke、Sato Toshiteru、Hayano Azusa、Takashima Yasuo
    • Journal Title

      Cancers

      Volume: 9 Issue: 8 Pages: 103-103

    • DOI

      10.3390/cancers9080103

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation-Induced Malignant Peripheral Nerve Sheath Tumors: A Systematic Review2017

    • Author(s)
      Yamanaka Ryuya、Hayano Azusa
    • Journal Title

      World Neurosurgery

      Volume: 105 Pages: 961-970

    • DOI

      10.1016/j.wneu.2017.06.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiation-Induced Schwannomas and Neurofibromas: A Systematic Review2017

    • Author(s)
      Yamanaka Ryuya、Hayano Azusa
    • Journal Title

      World Neurosurgery

      Volume: 104 Pages: 713-722

    • DOI

      10.1016/j.wneu.2017.05.066

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Secondary glioma following acute lymphocytic leukemia: Therapeutic implications.2017

    • Author(s)
      Yamanaka R, Hayano A
    • Journal Title

      Neurosurg Rev

      Volume: 40 Issue: 4 Pages: 549-557

    • DOI

      10.1007/s10143-016-0733-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiation-induced meningiomas: an exhaustive review of the literature.2017

    • Author(s)
      Yamanaka R, Hayano A, Kanayama T
    • Journal Title

      World Neurosurg

      Volume: 97 Pages: 635-644

    • DOI

      10.1016/j.wneu.2016.09.094

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiation-induced sarcomas of the central nervous system: a systematic review.2017

    • Author(s)
      Yamanaka R, Hayano A
    • Journal Title

      World Neurosurg

      Volume: 98 Pages: 818-828

    • DOI

      10.1016/j.wneu.2016.11.008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Secondary craniofacial sarcomas following retinoblastoma: a systematic review.2017

    • Author(s)
      Yamanaka R, Hayano A
    • Journal Title

      World Neurosurg

      Volume: in press Pages: 722-730

    • DOI

      10.1016/j.wneu.2017.02.031

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiation-induced schwannomas and neurofibromas: a systematic review.2017

    • Author(s)
      Yamanaka R, Hayano A
    • Journal Title

      World Neurosurg

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Late relapse of primary central nervous system lymphoma.2017

    • Author(s)
      Yamanaka R, Morii K, Shinbo Y, Sano M, Homma J, Tsuchiya N, Yajima N, Tsukamoto Y, Ogura R, Natsumeda M, Aoki H, Akiyama K, Saitoh T, Tamura T, Hondoh H, Kawaguchi A, Takahashi H, and Fujii Y
    • Journal Title

      Leukemia Lymphoma

      Volume: 58 Pages: 475-477

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term survivors of primary central nervous system lymphoma.2017

    • Author(s)
      Yamanaka R, Morii K, Sano M, Homma J, Yajima N, Tsukamoto Y, Ogura R, Natsumeda M, Aoki H, Akiyama K, Saitoh T, Hondoh H, Kawaguchi A, Takahashi H, Fujii Y.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 47 Issue: 2 Pages: 101-107

    • DOI

      10.1093/jjco/hyw171

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stat3 inhibitor abrogates the expression of PD-1 ligands on lymphoma cell lines2017

    • Author(s)
      Ma C, Horlad H, Pan C, Yano H, Ohnishi K, Fujiwara Y, Matsuoka M, Lee A, Niidome T, Yamanaka R, Takeya M, Komohara Y
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 57 Issue: 1 Pages: 21-25

    • DOI

      10.3960/jslrt.17006

    • NAID

      130005709510

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prognostic significance of S-phase fractions in peritumoral invading zone analyzed by laser scanning cytometry in patients with high-grade glioma (preliminary study).2016

    • Author(s)
      Nakajima S, Morii K, Takahashi H, Fujii Y, Yamanaka R
    • Journal Title

      ONCOLOGY LETTERS

      Volume: 11 Pages: 2106-2110

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiation-induced gliomas: A comprehensive review and meta-analysis.2016

    • Author(s)
      Yamanaka R, Hayano A, Kanayama T
    • Journal Title

      Neurosurg Rev

      Volume: in press Issue: 3 Pages: 719-731

    • DOI

      10.1007/s10143-016-0786-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 中枢神経系原発悪性リンパ腫におけるIon Reporterエクソームシーケンシングによる分子マーカー候補の同定2018

    • Author(s)
      高島康郎、佐々木泰史、早野あづさ、本間順平、深井順也、岩立康男、梶原浩司、石澤伸、本道洋昭、時野隆至、山中龍也
    • Organizer
      第77回日本癌学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] メトトレキサート耐性中枢神経原発悪性リンパ腫細胞株の樹立およびボルテゾミブ感受性の検討2018

    • Author(s)
      早野あづさ、高島康郎、山中龍也
    • Organizer
      第77回日本癌学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Expression analysis of N-oligosaccharides of glycoproteins in methotrexate-resistant central nervous system lymphoma cell lines.2018

    • Author(s)
      Takashima Y, Yoshimura T, Kano Y, Hayano A, Hondoh H, Ikenaka K, Yamanaka R
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳原発性および転移性脳悪性リンパ腫におけるProgrammed Cell Death Ligand 1 発 現の検討2017

    • Author(s)
      早野あづさ、菰原義弘、高島康郎、本間順平、深井順也、岩立康男、梶原浩司、石澤 伸、本道洋昭、山中龍也
    • Organizer
      第76回日本癌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] がん免疫療法のターゲットとなる分子と予後との関連の解析2017

    • Author(s)
      高島康郎、川口 淳、金山知彦、早野あづさ、山中龍也
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Whole-Genome Sequencing of Primary Central Nervous System Lymphoma and Diffuse Large B-Cell Lymphoma.2016

    • Author(s)
      Yoshida K, Yamanaka R and Ogawa S, et al.
    • Organizer
      58th ASH Annual Meeting and Exposition.
    • Place of Presentation
      San diego, CA,
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 中枢神経原発悪性リンパ腫におけるゲノム異常の全貌2016

    • Author(s)
      吉田健一、千葉健一、奥野友介、垣内伸之、鈴木啓道、白石友一、田中洋子、村垣善浩、椎名隆、宮野悟、千葉滋、山中 龍也、小川誠司
    • Organizer
      第75回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Book] Primary Central Nervous System Lymphoma (PCNSL): Incidence, Management and Outcomes,2016

    • Author(s)
      Kanayama T, Hayano A, Yamanaka R
    • Total Pages
      298
    • Publisher
      Nova Science Publishers,
    • Related Report
      2016 Research-status Report
  • [Book] Primary Central Nervous System Lymphoma (PCNSL): Incidence, Management and Outcomes,2016

    • Author(s)
      Yamanaka R
    • Total Pages
      298
    • Publisher
      Nova Science Publishers,
    • Related Report
      2016 Research-status Report
  • [Book] Primary Central Nervous System Lymphoma (PCNSL): Incidence, Management and Outcomes,2016

    • Author(s)
      Yamanaka R, Yoshioka S, Fujimoto S, Iwawaki Y
    • Total Pages
      298
    • Publisher
      Nova Science Publishers,
    • Related Report
      2016 Research-status Report
  • [Remarks] 京都府立医科大学 腫瘍分子標的治療学講座ホームページ

    • URL

      http://www.f.kpu-m.ac.jp/c/kouza/igaku/research.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都府立医科大学 医学研究科 腫瘍分子標的治療学講座HP

    • URL

      http://www.f.kpu-m.ac.jp/c/kouza/igaku

    • Related Report
      2017 Research-status Report 2016 Research-status Report

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

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