IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-17139-y.html
   My bibliography  Save this article

Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities

Author

Listed:
  • Sejin Oh

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Jeonghun Yeom

    (Center for Theragnosis, Korea Institute of Science and Technology
    Korea University of Science and Technology
    Convergence Medicine Research Center, Asan Institute for Life Sciences)

  • Hee Jin Cho

    (Institute for Refractory Cancer Research, Samsung Medical Center
    Precision Medicine Research Institute, Samsung Medical Center)

  • Ju-Hwa Kim

    (Yonsei University)

  • Seon-Jin Yoon

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Hakhyun Kim

    (Yonsei University College of Medicine)

  • Jason K. Sa

    (Korea University College of Medicine)

  • Shinyeong Ju

    (Center for Theragnosis, Korea Institute of Science and Technology
    Hanyang University)

  • Hwanho Lee

    (Yonsei University College of Medicine
    Yonsei University)

  • Myung Joon Oh

    (Yonsei University College of Medicine)

  • Wonyeop Lee

    (Hanyang University)

  • Yumi Kwon

    (Center for Theragnosis, Korea Institute of Science and Technology
    Hanyang University)

  • Honglan Li

    (Hanyang University
    Soongsil University)

  • Seunghyuk Choi

    (Hanyang University)

  • Jang Hee Han

    (Yonsei University College of Medicine
    Yonsei University Graduate School)

  • Jong Hee Chang

    (Yonsei University College of Medicine)

  • Eunsuk Choi

    (Institute for Refractory Cancer Research, Samsung Medical Center
    Sungkyunkwan University School of Medicine)

  • Jayeon Kim

    (Institute for Refractory Cancer Research, Samsung Medical Center
    Precision Medicine Research Institute, Samsung Medical Center)

  • Nam-Gu Her

    (Institute for Refractory Cancer Research, Samsung Medical Center)

  • Se Hoon Kim

    (Yonsei University College of Medicine)

  • Seok-Gu Kang

    (Yonsei University Graduate School
    Yonsei University College of Medicine)

  • Eunok Paek

    (Hanyang University)

  • Do-Hyun Nam

    (Institute for Refractory Cancer Research, Samsung Medical Center
    Sungkyunkwan University School of Medicine
    SAIHST, Sungkyunkwan University)

  • Cheolju Lee

    (Center for Theragnosis, Korea Institute of Science and Technology
    Korea University of Science and Technology
    KHU-KIST, Kyung Hee University)

  • Hyun Seok Kim

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

Abstract

The prognostic and therapeutic relevance of molecular subtypes for the most aggressive isocitrate dehydrogenase 1/2 (IDH) wild-type glioblastoma (GBM) is currently limited due to high molecular heterogeneity of the tumors that impedes patient stratification. Here, we describe a distinct binary classification of IDH wild-type GBM tumors derived from a quantitative proteomic analysis of 39 IDH wild-type GBMs as well as IDH mutant and low-grade glioma controls. Specifically, GBM proteomic cluster 1 (GPC1) tumors exhibit Warburg-like features, neural stem-cell markers, immune checkpoint ligands, and a poor prognostic biomarker, FKBP prolyl isomerase 9 (FKBP9). Meanwhile, GPC2 tumors show elevated oxidative phosphorylation-related proteins, differentiated oligodendrocyte and astrocyte markers, and a favorable prognostic biomarker, phosphoglycerate dehydrogenase (PHGDH). Integrating these proteomic features with the pharmacological profiles of matched patient-derived cells (PDCs) reveals that the mTORC1/2 dual inhibitor AZD2014 is cytotoxic to the poor prognostic PDCs. Our analyses will guide GBM prognosis and precision treatment strategies.

Suggested Citation

  • Sejin Oh & Jeonghun Yeom & Hee Jin Cho & Ju-Hwa Kim & Seon-Jin Yoon & Hakhyun Kim & Jason K. Sa & Shinyeong Ju & Hwanho Lee & Myung Joon Oh & Wonyeop Lee & Yumi Kwon & Honglan Li & Seunghyuk Choi & Ja, 2020. "Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17139-y
    DOI: 10.1038/s41467-020-17139-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-17139-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-17139-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Mykhaylo Slobodyanyuk & Alexander T. Bahcheli & Zoe P. Klein & Masroor Bayati & Lisa J. Strug & Jüri Reimand, 2024. "Directional integration and pathway enrichment analysis for multi-omics data," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17139-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.