title: Investigating molecular alterations to profile short- and long-term recurrence-free survival in patients with primary glioblastoma.
abstract: Glioblastoma (GB) is the most aggressive type of primary brain tumor. Despite the progress in recent years regarding the diagnosis and treatment of GB, the recurrence rate remains high, due to the infiltrative and dispersive nature of the tumor, which typically results in poor patient prognosis. In the present study, 19 formalin-fixed, paraffin-embedded GB samples were selected from patients with GB tumors. The samples were classified into a short or long recurrence-free survival (RFS) group, based on the time of first recurrence of the disease in the patients. The 19 samples were molecularly characterized for mutations in the isocitrate dehydrogenase 1 (IDH1) gene, amplification of the epidermal growth factor receptor (EGFR) gene, presence of the EGFR variant III, and methylation of the promoter region of the O6-methylguanine-DNA methyltransferase (MGMT) gene. Then, the expression of 84 genes involved in cell-cell and cell-matrix interactions, and that of 84 microRNAs (miRNAs) associated with brain cancer, was profiled. In addition, a copy number variation analysis of 23 genes reported to undergo frequent genomic alterations in human glioma was also performed. Differences in the expression levels of a number of genes were detected across the short and long RFS groups. Among these genes, 5 in particular were selected, and a 5-genes combination approach was developed, which was able to differentiate between patients with short and long RFS outcome. The high levels of sensitivity and precision displayed by this 5-genes combination approach, which were confirmed with a cross-validation method, provide a strong foundation for further validation of the involvement of the aforementioned genes in GB in a larger patient population. In conclusion, the present study has demonstrated how the expression pattern of miRNAs and mRNAs in patients with GB defines a particular molecular hallmark that may increase or reduce the aggressive behavior of GB tumors, thus influencing the survival rates of patients with GB, their response to therapy and their tendency to suffer a relapse.
authors.affiliation: Department of Translational Research and of New Surgical and Medical Technologies, University Hospital of Pisa, Pisa I-56126, Italy; Genomic Section, Pisa Science Foundation, Pisa I-56121, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Franceschi
authors.affiliation: Genomic Section, Pisa Science Foundation, Pisa I-56121, Italy.
authors.forename: Chiara M
authors.initials: CM
authors.lastname: Mazzanti
authors.affiliation: Genomic Section, Pisa Science Foundation, Pisa I-56121, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lessi
authors.affiliation: Genomic Section, Pisa Science Foundation, Pisa I-56121, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Aretini
authors.affiliation: Department of Translational Research and of New Surgical and Medical Technologies, University Hospital of Pisa, Pisa I-56126, Italy.
authors.forename: Francesco G
authors.initials: FG
authors.lastname: Carbone
authors.affiliation: Genomic Section, Pisa Science Foundation, Pisa I-56121, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: LA Ferla
authors.affiliation: Department of Translational Research and of New Surgical and Medical Technologies, University Hospital of Pisa, Pisa I-56126, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Scatena
authors.affiliation: Department of Translational Research and of New Surgical and Medical Technologies, University Hospital of Pisa, Pisa I-56126, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Ortenzi
authors.affiliation: Department of Neurosurgery, University Hospital of Pisa, Pisa I-56124, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Vannozzi
authors.affiliation: Department of Neurosurgery, University Hospital of Pisa, Pisa I-56124, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fanelli
authors.affiliation: Radiotherapy Unit, University Hospital of Pisa, Pisa I-56126, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasqualetti
authors.affiliation: Department of Translational Research and of New Surgical and Medical Technologies, University Hospital of Pisa, Pisa I-56126, Italy.
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.affiliation: Department of Translational Research and of New Surgical and Medical Technologies, University Hospital of Pisa, Pisa I-56126, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Zavaglia
authors.affiliation: Department of Translational Research and of New Surgical and Medical Technologies, University Hospital of Pisa, Pisa I-56126, Italy.
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Naccarato
keywords: gene expression; glioblastoma; molecular alterations; outcome prediction; recurrence