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Nat. Commun., Published: 03 July 2020, 11, Article number: 3288 (2020) | https://doi.org/10.1038/s41467-020-17139-y Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities

Sejin Oh^1,2,21, Jeonghun Yeom^3,4,5,21, Hee Jin Cho^6,7,21, Ju-Hwa Kim⁸, Seon-Jin Yoon^2,9, Hakhyun Kim², Jason K. Sa¹⁰, Shinyeong Ju^3,11, Hwanho Lee^2,12, Myung Joon Oh¹, Wonyeop Lee¹³, Yumi Kwon^3,11, Honglan Li^13,14, Seunghyuk Choi¹³, Jang Hee Han^1,15, Jong Hee Chang¹⁶, Eunsuk Choi^6,17, Jayeon Kim^6,7, Nam-Gu Her⁶, Se Hoon Kim¹⁸, Seok-Gu Kang^15,16, Eunok Paek^13,*, Do-Hyun Nam^6,17,19,*, Cheolju Lee^3,4,20,* & Hyun Seok Kim ^1,2,*

¹ Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
² Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
³ Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Korea.
⁴ Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, Korea.
⁵ Convergence Medicine Research Center, Asan Institute for Life Sciences, Seoul, Korea.
⁶ Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.
⁷ Precision Medicine Research Institute, Samsung Medical Center, Seoul, Korea.
⁸ Graduate Program for Nanomedical Science, Yonsei University, Seoul, Korea.
⁹ Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.
¹⁰ Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea.
¹¹ Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
¹² Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
¹³ Department of Computer Science, Hanyang University, Seoul, Korea.
¹⁴ School of Computer Science and Engineering, Soongsil University, Seoul, Korea.
¹⁵ Department of Medical Science, Yonsei University Graduate School, Seoul, Korea.
¹⁶ Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
¹⁷ Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
¹⁸ Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
¹⁹ Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
²⁰ Department of Converging Science and Technology, KHU-KIST, Kyung Hee University, Seoul, Korea.

²¹ These authors contributed equally: Sejin Oh, Jeonghun Yeom, Hee Jin Cho.

^*Corresponding author

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.

논문정보

형식Research article
게재일2020년 07월 (BRIC 등록일 2020-07-07)
연구진국내 연구진
분야 의약학 > 종양의학

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