TY - JOUR
T1 - A Molecular Signature associated with prolonged survival in Glioblastoma patients treated with Regorafenib
AU - Santangelo, Alessandra
AU - Rossato, Marzia
AU - Lombardi, Giuseppe
AU - Benfatto, Salvatore
AU - Lavezzari, Denise
AU - De Salvo, Gian Luca
AU - Indraccolo, Stefano
AU - Dechecchi, Maria Cristina
AU - Prandini, Paola
AU - Gambari, Roberto
AU - Scapoli, Chiara
AU - Di Gennaro, Gianfranco
AU - Caccese, Mario
AU - Eoli, Marica
AU - Rudà, Roberta
AU - Brandes, Alba Ariela
AU - Ibrahim, Toni
AU - Rizzato, Simona
AU - Lolli, Ivan
AU - Lippi, Giuseppe
AU - Delledonne, Massimo
AU - Zagonel, Vittorina
AU - Cabrini, Giulio
N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2020/7/14
Y1 - 2020/7/14
N2 - 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, miR-222-3p) 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, miR-301a-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.
AB - 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, miR-222-3p) 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, miR-301a-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.
U2 - 10.1093/neuonc/noaa156
DO - 10.1093/neuonc/noaa156
M3 - Article
C2 - 32661549
VL - 1
JO - Neuro-Oncology
JF - Neuro-Oncology
SN - 1522-8517
IS - 13
M1 - noaa156
ER -