title: Metabolic/Proteomic Signature Defines Two Glioblastoma Subtypes With Different Clinical Outcome.
abstract: Glioblastoma (GBM) is one of the deadliest human cancers. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant subclassification systems. Analyzing a collection of seventeen patient-derived glioblastoma stem-like cells (GSCs) by gene expression profiling, NMR spectroscopy and signal transduction pathway activation, we identified two GSC clusters, one characterized by a pro-neural-like phenotype and the other showing a mesenchymal-like phenotype. Evaluating the levels of proteins differentially expressed by the two GSC clusters in the TCGA GBM sample collection, we found that SRC activation is associated with a GBM subgroup showing better prognosis whereas activation of RPS6, an effector of mTOR pathway, identifies a subgroup with a worse prognosis. The two clusters are also differentiated by NMR spectroscopy profiles suggesting a potential prognostic stratification based on metabolic evaluation. Our data show that the metabolic/proteomic profile of GSCs is informative of the genomic/proteomic GBM landscape, which differs among tumor subtypes and is associated with clinical outcome.
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: G
authors: G
authors: Marziali
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: M
authors: M
authors: Signore
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: M
authors: M
authors: Buccarelli
authors: Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy.
authors: S
authors: S
authors: Grande
authors: Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy.
authors: A
authors: A
authors: Palma
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: M
authors: M
authors: Biffoni
authors: Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy.
authors: A
authors: A
authors: Rosi
authors: nstitute of Neurosurgery, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Q G
authors: QG
authors: D'Alessandris
authors: Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: M
authors: M
authors: Martini
authors: Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: L M
authors: LM
authors: Larocca
authors: Regina Elena National Cancer Institute, Rome, Italy.
authors: R
authors: R
authors: De Maria
authors: nstitute of Neurosurgery, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: R
authors: R
authors: Pallini
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: L
authors: L
authors: Ricci-Vitiani
mesh_terms: D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D040901:Proteomics; D015996:Survival Rate
chemical_list: D009363:Neoplasm Proteins