Alessandra Santangelo1, Marzia Rossato2, Giuseppe Lombardi3, Salvatore Benfatto2, Denise Lavezzari2, Gian Luca De Salvo4, Stefano Indraccolo5, Maria Cristina Dechecchi1, Paola Prandini1, Roberto Gambari6, Chiara Scapoli6, Gianfranco Di Gennaro7, Mario Caccese3, Marica Eoli8, Roberta Rudà9, Alba Ariela Brandes10, Toni Ibrahim11, Simona Rizzato12, Ivan Lolli13, Giuseppe Lippi1, Massimo Delledonne2, Vittorina Zagonel3, Giulio Cabrini1,6. 1. Department of Neurosciences, Biomedicine, and Movement, University of Verona, Verona, Italy. 2. Department of Biotechnology, University of Verona, Verona, Italy. 3. Department of Oncology, Veneto Institute of Oncology (IOV), Scientific Institute for Research, Hospitalization, and Health Care (IRCCS), Padova, Italy. 4. Research Unit, IOV-IRCCS, Padova, Italy. 5. Basic and Translational Oncology Unit, IOV-IRCCS, Padova, Italy. 6. Department of Life Sciences and Biotechnologies, University of Ferrara, Ferrara, Italy. 7. Laboratory of Clinical Biochemistry, University Hospital of Verona, Verona, Italy. 8. Molecular Neuro-Oncology Unit, Carlo Besta Neurological Institute Foundation, Milan, Italy. 9. Department of Neuro-Oncology, University of Turin and City of Health and Science Hospital, Turin, Italy. 10. Medical Oncology Department, Local Health Unit, IRCCS Institute of Neurological Sciences, Bologna, Italy. 11. Osteo-oncology and Rare Tumors Center, Romagna Scientific Institute for the Study and Treatment of Cancer, IRCCS, Meldola, Italy. 12. Department of Oncology, Friuli-Venezia Giulia University Hospital, Udine, Italy. 13. Medical Oncology Unit, IRCCS Saverio de Bellis Hospital, Castellana Grotte, Bari, Italy.
Abstract
BACKGROUND: Patients with glioblastoma (GBM) have a dramatically poor prognosis. The recent REGOMA trial suggested an overall survival (OS) 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 micro (mi)RNA profiles were associated with patients' OS and progression-free survival. RESULTS: In the 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. In the second step, a mini-signature of 2 gene transcripts (HIF1A, CDKN1A) and 3 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 mo). CONCLUSIONS: The study provides evidence that a signature based on the expression of 5 biomarkers could help identify a subgroup of GBM patients exhibiting a striking survival advantage when treated with regorafenib. Although the presented results must be confirmed in larger replication cohorts, the study highlights potential biomarker options to help guide the clinical decision among regorafenib and other treatments in patients with relapsing GBM.
BACKGROUND:Patients with glioblastoma (GBM) have a dramatically poor prognosis. The recent REGOMA trial suggested an overall survival (OS) 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 micro (mi)RNA profiles were associated with patients' OS and progression-free survival. RESULTS: In the 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. In the second step, a mini-signature of 2 gene transcripts (HIF1A, CDKN1A) and 3 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 mo). CONCLUSIONS: The study provides evidence that a signature based on the expression of 5 biomarkers could help identify a subgroup of GBM patients exhibiting a striking survival advantage when treated with regorafenib. Although the presented results must be confirmed in larger replication cohorts, the study highlights potential biomarker options to help guide the clinical decision among regorafenib and other treatments in patients with relapsing GBM.
Authors: Nathaniel H Boyd; Kiera Walker; Joshua Fried; James R Hackney; Paul C McDonald; Gloria A Benavides; Raffaella Spina; Alessandra Audia; Sarah E Scott; Catherine J Landis; Anh Nhat Tran; Mark O Bevensee; Corinne Griguer; Susan Nozell; G Yancey Gillespie; Burt Nabors; Krishna P Bhat; Eli E Bar; Victor Darley-Usmar; Bo Xu; Emily Gordon; Sara J Cooper; Shoukat Dedhar; Anita B Hjelmeland Journal: JCI Insight Date: 2017-12-21
Authors: Urška Verbovšek; Helena Motaln; Ana Rotter; Nadia A Atai; Kristina Gruden; Cornelis J F Van Noorden; Tamara T Lah Journal: PLoS One Date: 2014-10-30 Impact factor: 3.240
Authors: Andrés F Cardona; Daniel Jaramillo-Velásquez; Alejandro Ruiz-Patiño; Carolina Polo; Enrique Jiménez; Fernando Hakim; Diego Gómez; Juan Fernando Ramón; Hernando Cifuentes; Juan Armando Mejía; Fernando Salguero; Camila Ordoñez; Álvaro Muñoz; Sonia Bermúdez; Nicolas Useche; Diego Pineda; Luisa Ricaurte; Zyanya Lucia Zatarain-Barrón; July Rodríguez; Jenny Avila; Leonardo Rojas; Elvira Jaller; Carolina Sotelo; Juan Esteban Garcia-Robledo; Nicolas Santoyo; Christian Rolfo; Rafael Rosell; Oscar Arrieta Journal: J Neurooncol Date: 2021-09-09 Impact factor: 4.130