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Oh, Sejin; Yeom, Jeonghun; Cho, Hee Jin; Kim, Ju-Hwa; Yoon, Seon-Jin; Kim, Hakhyun; Sa, Jason K.; Ju, Shinyeong; Lee, Hwanho; Oh, Myung Joon; Lee, Wonyeop; Kwon, Yumi; Li, Honglan; Choi, Seunghyuk; Han, Jang Hee; Chang, Jong Hee; Choi, Eunsuk; Kim, Jayeon; Her, Nam-Gu; Kim, Se Hoon; Kang, Seok-Gu; Paek, Eunok; Nam, Do-Hyun; Lee, Cheolju; Kim, Hyun Seok
Nature communications, 07/2020, Letnik: 11, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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