Comparative analysis of deeply phenotyped GBM cohorts of ‘short-term’ and ‘long-term’ survivors
Author:
Biswas Archita1, Salvucci Manuela1, Connor Kate1, Düssmann Heiko1, Carberry Steven1, Fichtner Michael1, King Ellen1, Murphy Brona1, O’Farrell A.C1, Cryan Jane2, Beausang Alan2, Heffernan Josephine2, Cremona Mattia3, Hennessy Bryan T.3, Clerkin James3, Sweeney Kieron J.2, MacNally Steve2, Brett F2, O’Halloran P2, Bacon Orna1, Furney Simon1, Verreault Maite4, Quissac Emie4, Bielle Franck4, Ahmed Mohammed H4, Idbaih Ahmed4, Leenstra Sieger5, Ntafoulis Ioannis5, Fabro Federica5, Lamfers Martine5, Golebiewska Anna6, Hertel Frank6, Niclou Simone P6, Yen Romain Tching Chi7, Kremer Andreas7, Dilcan Gonca8, Lodi Francesca8, Arijs Ingrid8, Lambrechts Diether8, P Manasa Kalya9, Kel Alexander9, Byrne Annette T1, Prehn Jochen H.M1
Affiliation:
1. Royal College of Surgeons in Ireland 2. Beaumont Hospital 3. Royal College of Surgeons in Ireland and Beaumont Hospital 4. Sorbonne Université, AP-HP, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix 5. Erasmus University Medical Center 6. Luxembourg Institute of Health 7. Information Technology for Translational Medicine (ITTM) 8. VIB-KU Leuven Center for Brain & Disease Research 9. geneXplain GmbH
Abstract
Abstract
Glioblastoma (GBM) is an aggressive brain cancer that typically results in death in the first 15 months after diagnosis. There have been limited advances in finding new treatments for GBM. In this study, we investigated molecular differences between patients with extremely short (≤9 months, Short term survivors, STS) and long survival (≥36 months, Long term survivors, LTS). Patients were selected from an in-house cohort (GLIOTRAIN-cohort), using defined inclusion criteria (Karnofsky score >70; age <70 years old; Stupp protocol as first line treatment, IDH wild type), and a multi-omic analysis of LTS and STS GBM samples was performed. Transcriptomic analysis of tumour samples identified cilium gene signatures enriched in LTSs. Immunohistochemical analysis confirmed the presence of cilia in the tumours of LTSs. Notably, reverse phase protein array analysis (RPPA) demonstrated increased phosphorylated GAB1 (Y627), SRC (Y527), BCL2 (S70) and RAF (S338) protein expression in STS compared to LTS. We identified 25 unique master regulators (MR) and 13 transcription factors (TFs) belonging to ontologies of integrin signalling and cell cycle to be upregulated in STS. These data deliver new potential biomarkers and therapeutic targets for the management of GBM.
Publisher
Research Square Platform LLC
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