Comparative analysis of deeply phenotyped GBM cohorts of 'short-term' and 'long-term' survivors
Background: 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).
Methods: 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.
Results: Transcriptomic analysis of tumour samples identified cilium gene signatures as enriched in LTS. Moreover, Immunohistochemical analysis confirmed the presence of cilia in the tumours of LTS. 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. Next, 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.
Conclusion: Overall, comparison of STS and LTS GBM patients, identifies novel biomarkers and potential actionable therapeutic targets for the management of GBM.
European Union’s Horizon 2020 and Horizon Europe research and innovation programme under the Marie Skłodowska-Curie ITN / Doctoral Network initiatives (Grant Agreement #s 766069 ‘GLIOTRAIN’ and 101073386 ‘GLIORESOLVE’)
Brain Tumour Ireland to the Beaumont Hospital Brain Tumour Bioresource, the contribution of the Clinical and Epidemiological Investigation Center, Department of Population Health, Luxembourg Institute of Health
Open Access funding provided by the IReL Consortium
CommentsThe original article is available at https://link.springer.com/
Published CitationBiswas A. et al. Comparative analysis of deeply phenotyped GBM cohorts of 'short-term' and 'long-term' survivors. J Neurooncol. 2023;163(2):327-338
Publication Date26 May 2023
- Beaumont Hospital
- Centre for Systems Medicine
- Physiology and Medical Physics
- Published Version (Version of Record)