Comparative analysis of deeply phenotyped GBM cohorts of 'short-term' and 'long-term' survivors

对“短期”和“长期”幸存者的深度表型胶质母细胞瘤队列进行比较分析

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作者:Archita Biswas, Manuela Salvucci, Kate Connor, Heiko Düssmann, Steven Carberry, Michael Fichtner, Ellen King, Brona Murphy, Alice C O'Farrell, Jane Cryan, Alan Beausang, Josephine Heffernan, Mattia Cremona, Bryan T Hennessy, James Clerkin, Kieron J Sweeney, Steve MacNally, Francesca Brett, Philip O'

Background

Glioblastoma (GBM) is an aggressive brain cancer that typically

Conclusion

Overall, comparison of STS and LTS GBM patients, identifies novel biomarkers and potential actionable therapeutic targets for the management of GBM.

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.

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