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

Abstract

// Barbara Fazi 1 , Armando Felsani 2, 3 , Luigi Grassi 4 , Anna Moles 2, 3 , Daniel D’Andrea 4 , Nicola Toschi 1, 5, 6 , Daria Sicari 1 , Pasquale De Bonis 7, 8 , Carmelo Anile 7 , Maria Giovanna Guerrisi 4 , Emilia Luca 9 , Maria Giulia Farace 1 , Giulio Maira 7 , Silvia Anna Ciafré 1, * , Annunziato Mangiola 7, * 1 Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy 2 CNR, Institute of Cell Biology and Neurobiology, Rome, Italy 3 Genomnia srl, Lainate, Milan, Italy 4 Department of Physics, University of Rome “La Sapienza”, Rome, Italy 5 Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA 6 Harvard Medical School, Boston, MA, USA 7 Department of Head and Neck, Institute of Neurosurgery, Catholic University of Sacred Heart, Rome, Italy 8 Neurosurgery, Ferrara University Hospital S. Anna, Cona di Ferrara, Ferrara, Italy 9 Institute of Anatomic Pathology, University Hospital “A. Gemelli”, Catholic University of Sacred Heart, Rome, Italy * These authors have contributed equally to this work Correspondence to: Silvia Anna Ciafrè, e-mail: ciafre@uniroma2.it Keywords: glioblastoma, microRNA, TGFβ, peritumoral area, editing Received: January 22, 2015      Accepted: May 18, 2015      Published: June 01, 2015 ABSTRACT 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.