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.

A Molecular Signature associated with prolonged survival in Glioblastoma patients treated with Regorafenib

Gambari, Roberto;Scapoli, Chiara;Cabrini, Giulio
Ultimo
2021

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, 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.
2021
Santangelo, Alessandra; Rossato, Marzia; Lombardi, Giuseppe; Benfatto, Salvatore; Lavezzari, Denise; De Salvo, Gian Luca; Indraccolo, Stefano; Dechecc...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2440276
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