Studio finanziato dalla Brain Research Foundation Verona.
Articolo pubblicato online il 14 luglio 2020: https://doi.org/10.1093/neuonc/noaa156
© The Author(s) 2020. Pubblicato da Oxford University Press a nome di Society for Neuro-Oncology. Tutti i diritti riservati. Per le autorizzazioni, inviare un’e-mail a: journals.permissions@oup.com.
Autori
Alessandra Santangelo, Marzia Rossato, Giuseppe Lombardi, Salvatore Benfatto, Denise Lavezzari, Gian Luca De Salvo, Stefano Indraccolo, Maria Cristina Dechecchi, Paola Prandini, Roberto Gambari, Chiara Scapoli, Gianfranco Di Gennaro, Mario Caccese, Marica Eoli, Roberta Rudà, Alba Ariela Brandes, Toni Ibrahim, Simona Rizzato, Ivan Lolli, Giuseppe Lippi, Massimo Delledonne, Vittorina Zagonel, Giulio Cabrini.
Abstract
Background: Patients with glioblastoma (GBM) have a dramatically poor prognosis. The recent REGOMA trial suggested an overall survival benefit of regorafenib in recurrent GBM patients. Considering the extreme genetic heterogeneity of GBMs, we aimed to identify molecular biomarkers predictive of differential response to the drug.
Methods: Total RNA was extracted from tumor samples of patients enrolled in the REGOMA trial. Genome-wide transcriptome and miRNA profiles were associated with patients’ Overall Survival (OS) and Progression Free Survival (PFS).
Results: At first step, a set of 11 gene transcripts (HIF1A, CTSK, SLC2A1, KLHL12, CDKN1A, CA12, WDR1, CD53, CBR4, NIFK-AS1, RAB30-DT) and 10 miRNAs (miR-93-5p, miR-203a-3p, miR-17-5p, let-7c-3p, miR-101-3p, miR-3607-3p, miR-6516-3p, miR-301a-3p, miR-23b-3p, miR222-3p) was filtered by comparing survival between regorafenib and lomustine arms. As second step, a minisignature of two gene transcripts (HIF1A, CDKN1A) and three miRNAs (miR-3607-3p, miR301a-3p, miR-93-5p) identified a subgroup of patients showing prolonged survival after regorafenib administration (median OS range 10.6 – 20.8 months).
Conclusions: The study provides evidence that a signature based on the expression of five biomarkers could help identifying a subgroup of GBM patients exhibiting a striking survival advantage when treated with regorafenib. Despite the presented results must be confirmed in larger replication cohorts, the study highlights potential biomarker options to help guiding the clinical decision among regorafenib and other treatments in patients with relapsing GBM.
Responsabile: Giulio Cabrini – Università degli Studi di Verona
giulio.cabrini@univr.it