Molecular subclassification of glioblastoma based on the absolute quantitative proteomics

• Project/Area Number: 26670638
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Kanazawa University
• Principal Investigator: NAKADA MITSUTOSHI 金沢大学, 医学系, 教授 (20334774)
• Co-Investigator(Renkei-kenkyūsha): TERASAKI TETSUYA 東北大学, 薬学部, 教授 (60155463)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 膠芽腫 / プロテオミクス / チロシンキナーゼ / 分類

Outline of Final Research Achievements

The purpose of this study is to attempt to classify GBM subtypes based on the molecular profile determined by absolute quantitative proteomics and to investigate its clinical significance. GBMs in our study harbored mutually exclusive dominant expression of three RTKs; EGFR, PDGFRα and ERBB2. Therefore, we propose a subclassification of GBM with respect to the dominant expression of these proteins; EGFR (n=25), PDGFRα (n=11) and ERBB2 (n=7). PFS and OS tended to be longer in ERBB2 group in comparison with EGFR and PDGFRα group. Molecular subclassification of GBM based on the absolute quantitative proteomics reflects the clinical behavior and might have clinical significance.

Research Products

• [Journal Article] Serine/Threonine kinase MLK4 determines Mesenchymal Identity in Glioma Stem Cells in an NFkB-dependent manner (2016)
  • Author(s): Kim SH, Ezhilarasan R, Chhipa R, Ladner K, Phillips E, Sparks A, Taylor D, Furuta T, Sabit H, Kurozumi K, Kuroiwa T, Akio A, Gallego-Perez1 D, Sulman EP, Cheng S, Lee J, Nakada M, Guttridge D, DasGupta B, Goidts V, Bhat KP, Walker J, Nakano I.
  • Journal Title: Cancer Cell Volume: 29 Issue: 2 Pages: 201-213
  • DOI: 10.1016/j.ccell.2016.01.005
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells. (2015)
  • Author(s): Tanaka S, Nakada M, Yamada D, Nakano I, Todo T, Ino Y, Hoshii T, Tadokoro Y, Ohta K, Ali MA, Hayashi Y, Hamada J, Hirao A.
  • Journal Title: J Neurooncol. Volume: 121 Issue: 2 Pages: 239-50
  • DOI: 10.1007/s11060-014-1630-z
  • Peer Reviewed / Open Access
• [Journal Article] Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1 and c-Jun N-terminal kinase-mediated pathway. (2015)
  • Author(s): Chikano Y, Domoto T, Furuta T, Sabit H, Kitano-Tamura A, Ilya V. Pyko, Takino T, Sai Y, Hayashi Y, Sato H, Miyamoto K, Nakada M, MinamotoT.
  • Journal Title: Molecular Cancer Therapeutics Volume: 14 Issue: 2 Pages: 564-574
  • DOI: 10.1158/1535-7163.mct-14-0479
  • Peer Reviewed / Open Access
• [Presentation] Biomarkers of glioblastoma identified by quantitative proteomics with SWATH mass spectrometry. (2016)
  • Author(s): Nakada M, Miyauchi E, Tachikawa M, Furuta T, Sabit H, Ohtsuki S, Terasaki T.
  • Organizer: The 21st International Conference on Brain Tumor Research & Therapy
  • Place of Presentation: Bankoku Shinryokan (Okinawa)
  • Year and Date: 2016-04-10
  • Int'l Joint Research
• [Presentation] 最先端プロテオミクスSWATH法による膠芽腫バイオマーカーの探索 (2015)
  • Author(s): 中田光俊，宮内英輔、立川正憲、古田拓也、淑瑠ヘムラサビット，大槻純男、寺崎哲也
  • Organizer: 第16回日本分子脳神経外科学会
  • Place of Presentation: アクトシティ浜松コングレスセンター（浜松）
  • Year and Date: 2015-08-28
• [Presentation] Molecular subclassification of glioblastoma based on the absolute quantitative proteomics. (2014)
  • Author(s): Nakada M, Obuchi W, Ohtsuki S, Tanaka S, Furuta T, Kitabayashi T, Sabit H, Terasaki T, Hayashi Y.
  • Organizer: Society for Neuro-Oncology 19th Annual Meeting 2014
  • Place of Presentation: Loews Miami Beach Hotel (Miami, Florida, USA)
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] 絶対定量プロテオミクスによる新規膠芽腫サブタイプ分類の臨床的有用性の検討 (2014)
  • Author(s): 中田光俊，田中慎吾，小渕 航，大槻純男，古田拓也，宮下勝吉，寺崎哲也，林 裕
  • Organizer: 第15回日本分子脳神経外科学会
  • Place of Presentation: 山形（大手門パルズ）
  • Year and Date: 2014-09-25 – 2014-09-26
• [Remarks] 金沢大学脳神経外科
  • URL: http://neurosurgery.w3.kanazawa-u.ac.jp/