Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities
| العنوان: | Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities |
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| المؤلفون: | Se Hoon Kim, Wonyeop Lee, Honglan Li, Jason K. Sa, Hyun Seok Kim, Seunghyuk Choi, Jayeon Kim, Yumi Kwon, Oh Sejin, Ju Hwa Kim, Nam Gu Her, Jang Hee Han, Shinyeong Ju, Hwanho Lee, Cheolju Lee, Eunok Paek, Eunsuk Choi, Jeonghun Yeom, Myung Joon Oh, Do-Hyun Nam, Hee Jin Cho, Hakhyun Kim, Jong Hee Chang, Seon Jin Yoon, Seok Gu Kang |
| المصدر: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Proteomics, Cell Survival, Science, Morpholines, General Physics and Astronomy, Proteomic analysis, mTORC1, Kaplan-Meier Estimate, Mechanistic Target of Rapamycin Complex 2, Biology, Mechanistic Target of Rapamycin Complex 1, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Glioma, Cell Line, Tumor, medicine, Biomarkers, Tumor, Humans, Phosphoglycerate dehydrogenase, lcsh:Science, neoplasms, Protein Kinase Inhibitors, Proteogenomics, Multidisciplinary, Brain Neoplasms, Wild type, General Chemistry, medicine.disease, Prognosis, Immune checkpoint, Isocitrate Dehydrogenase, nervous system diseases, CNS cancer, 030104 developmental biology, Isocitrate dehydrogenase, FKBP, Pyrimidines, 030220 oncology & carcinogenesis, Benzamides, Mutation, Cancer research, lcsh:Q, Glioblastoma |
| الوصف: | 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. The heterogeneity of IDH1/2 wild-type glioblastoma limits its prognosis and therapy. Here, the authors show a binary stratification, based on quantitative proteomic analysis of samples from patients with glioblastoma, with different prognosis and therapeutic vulnerabilities. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3e882ba4c93bcaca33a47d1e76ca4db http://europepmc.org/articles/PMC7335111 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b3e882ba4c93bcaca33a47d1e76ca4db |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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