The transcriptome and miRNome profiling of glioblastoma tissues and peritumoral regions highlights molecular pathways shared by tumors and surrounding areas and reveals differences between short-term and long-term survivors
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Barbara Fazi1, Armando Felsani2,3, Luigi Grassi4, Anna Moles2,3, Daniel D’Andrea4, Nicola Toschi1,5,6, Daria Sicari1, Pasquale De Bonis7,8, Carmelo Anile7, Maria Giovanna Guerrisi4, Emilia Luca9, Maria Giulia Farace1, Giulio Maira7, Silvia Anna Ciafré1,*, Annunziato Mangiola7,*
1Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy
2CNR, Institute of Cell Biology and Neurobiology, Rome, Italy
3Genomnia srl, Lainate, Milan, Italy
4Department of Physics, University of Rome “La Sapienza”, Rome, Italy
5Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA
6Harvard Medical School, Boston, MA, USA
7Department of Head and Neck, Institute of Neurosurgery, Catholic University of Sacred Heart, Rome, Italy
8Neurosurgery, Ferrara University Hospital S. Anna, Cona di Ferrara, Ferrara, Italy
9Institute of Anatomic Pathology, University Hospital “A. Gemelli”, Catholic University of Sacred Heart, Rome, Italy
*These authors have contributed equally to this work
Silvia Anna Ciafrè, e-mail: [email protected]
Keywords: glioblastoma, microRNA, TGFβ, peritumoral area, editing
Received: January 22, 2015 Accepted: May 18, 2015 Published: June 01, 2015
Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor, driving patients to death within 15 months after diagnosis (short term survivors, ST), with the exception of a small fraction of patients (long term survivors, LT) surviving longer than 36 months. Here we present deep sequencing data showing that peritumoral (P) areas differ from healthy white matter, but share with their respective frankly tumoral (C) samples, a number of mRNAs and microRNAs representative of extracellular matrix remodeling, TGFβ and signaling, of the involvement of cell types different from tumor cells but contributing to tumor growth, such as microglia or reactive astrocytes. Moreover, we provide evidence about RNAs differentially expressed in ST vs LT samples, suggesting the contribution of TGF-β signaling in this distinction too. We also show that the edited form of miR-376c-3p is reduced in C vs P samples and in ST tumors compared to LT ones. As a whole, our study provides new insights into the still puzzling distinction between ST and LT tumors, and sheds new light onto that “grey” zone represented by the area surrounding the tumor, which we show to be characterized by the expression of several molecules shared with the proper tumor mass.
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