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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Marziali G,Signore M,Buccarelli M,Grande S,Palma A,Biffoni M,Rosi A,D'Alessandris QG,Martini M,Larocca LM,De Maria R,Pallini R,Ricci-Vitiani L

doi

10.1038/srep21557

subject

Has Abstract

pub_date

2016-02-09 00:00:00

pages

21557

issn

2045-2322

pii

srep21557

journal_volume

6

pub_type

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