Investigating molecular alterations to profile short- and long-term recurrence-free survival in patients with primary glioblastoma

Franceschi,Sara; Mazzanti,Chiara  M.; Lessi,Francesca; Aretini,Paolo; Carbone,Francesco  G.; La Ferla,Marco; Scatena,Cristian; Ortenzi,Valerio; Vannozzi,Riccardo; Fanelli,Giovanni; Pasqualetti,Francesco; Bevilacqua,Generoso; Zavaglia,Katia; Naccarato,Antonio  G.

doi:10.3892/ol.2015.3738

Investigating molecular alterations to profile short- and long-term recurrence-free survival in patients with primary glioblastoma

Authors:
- Sara Franceschi
- Chiara M. Mazzanti
- Francesca Lessi
- Paolo Aretini
- Francesco G. Carbone
- Marco La Ferla
- Cristian Scatena
- Valerio Ortenzi
- Riccardo Vannozzi
- Giovanni Fanelli
- Francesco Pasqualetti
- Generoso Bevilacqua
- Katia Zavaglia
- Antonio G. Naccarato
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Affiliations: 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, Department of Neurosurgery, University Hospital of Pisa, Pisa I‑56124, Italy, Radiotherapy Unit, University Hospital of Pisa, Pisa I‑56126, Italy
Published online on: September 23, 2015 https://doi.org/10.3892/ol.2015.3738
Pages: 3599-3606

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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.

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