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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 mon...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322749/ https://www.ncbi.nlm.nih.gov/pubmed/37237151 http://dx.doi.org/10.1007/s11060-023-04341-3 |
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author | Biswas, Archita Salvucci, Manuela Connor, Kate Düssmann, Heiko Carberry, Steven Fichtner, Michael King, Ellen Murphy, Brona O’Farrell, Alice C. Cryan, Jane Beausang, Alan Heffernan, Josephine Cremona, Mattia Hennessy, Bryan T. Clerkin, James Sweeney, Kieron J. MacNally, Steve Brett, Francesca O’Halloran, Philip Bacon, Orna Furney, Simon Verreault, Maite Quissac, Emie Bielle, Franck Ahmed, Mohammed H. Idbaih, Ahmed Leenstra, Sieger Ntafoulis, Ioannis Fabro, Federica Lamfers, Martine Golebiewska, Anna Hertel, Frank Niclou, Simone P. Yen, Romain Tching Chi Kremer, Andreas Dilcan, Gonca Lodi, Francesca Arijs, Ingrid Lambrechts, Diether Purushothama, Manasa Kalya Kel, Alexander Byrne, Annette T. Prehn, Jochen H.M. |
author_facet | Biswas, Archita Salvucci, Manuela Connor, Kate Düssmann, Heiko Carberry, Steven Fichtner, Michael King, Ellen Murphy, Brona O’Farrell, Alice C. Cryan, Jane Beausang, Alan Heffernan, Josephine Cremona, Mattia Hennessy, Bryan T. Clerkin, James Sweeney, Kieron J. MacNally, Steve Brett, Francesca O’Halloran, Philip Bacon, Orna Furney, Simon Verreault, Maite Quissac, Emie Bielle, Franck Ahmed, Mohammed H. Idbaih, Ahmed Leenstra, Sieger Ntafoulis, Ioannis Fabro, Federica Lamfers, Martine Golebiewska, Anna Hertel, Frank Niclou, Simone P. Yen, Romain Tching Chi Kremer, Andreas Dilcan, Gonca Lodi, Francesca Arijs, Ingrid Lambrechts, Diether Purushothama, Manasa Kalya Kel, Alexander Byrne, Annette T. Prehn, Jochen H.M. |
author_sort | Biswas, Archita |
collection | PubMed |
description | 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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-023-04341-3. |
format | Online Article Text |
id | pubmed-10322749 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-103227492023-07-07 Comparative analysis of deeply phenotyped GBM cohorts of ‘short-term’ and ‘long-term’ survivors Biswas, Archita Salvucci, Manuela Connor, Kate Düssmann, Heiko Carberry, Steven Fichtner, Michael King, Ellen Murphy, Brona O’Farrell, Alice C. Cryan, Jane Beausang, Alan Heffernan, Josephine Cremona, Mattia Hennessy, Bryan T. Clerkin, James Sweeney, Kieron J. MacNally, Steve Brett, Francesca O’Halloran, Philip Bacon, Orna Furney, Simon Verreault, Maite Quissac, Emie Bielle, Franck Ahmed, Mohammed H. Idbaih, Ahmed Leenstra, Sieger Ntafoulis, Ioannis Fabro, Federica Lamfers, Martine Golebiewska, Anna Hertel, Frank Niclou, Simone P. Yen, Romain Tching Chi Kremer, Andreas Dilcan, Gonca Lodi, Francesca Arijs, Ingrid Lambrechts, Diether Purushothama, Manasa Kalya Kel, Alexander Byrne, Annette T. Prehn, Jochen H.M. J Neurooncol Research 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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-023-04341-3. Springer US 2023-05-26 2023 /pmc/articles/PMC10322749/ /pubmed/37237151 http://dx.doi.org/10.1007/s11060-023-04341-3 Text en © The Author(s) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Biswas, Archita Salvucci, Manuela Connor, Kate Düssmann, Heiko Carberry, Steven Fichtner, Michael King, Ellen Murphy, Brona O’Farrell, Alice C. Cryan, Jane Beausang, Alan Heffernan, Josephine Cremona, Mattia Hennessy, Bryan T. Clerkin, James Sweeney, Kieron J. MacNally, Steve Brett, Francesca O’Halloran, Philip Bacon, Orna Furney, Simon Verreault, Maite Quissac, Emie Bielle, Franck Ahmed, Mohammed H. Idbaih, Ahmed Leenstra, Sieger Ntafoulis, Ioannis Fabro, Federica Lamfers, Martine Golebiewska, Anna Hertel, Frank Niclou, Simone P. Yen, Romain Tching Chi Kremer, Andreas Dilcan, Gonca Lodi, Francesca Arijs, Ingrid Lambrechts, Diether Purushothama, Manasa Kalya Kel, Alexander Byrne, Annette T. Prehn, Jochen H.M. Comparative analysis of deeply phenotyped GBM cohorts of ‘short-term’ and ‘long-term’ survivors |
title | Comparative analysis of deeply phenotyped GBM cohorts of ‘short-term’ and ‘long-term’ survivors |
title_full | Comparative analysis of deeply phenotyped GBM cohorts of ‘short-term’ and ‘long-term’ survivors |
title_fullStr | Comparative analysis of deeply phenotyped GBM cohorts of ‘short-term’ and ‘long-term’ survivors |
title_full_unstemmed | Comparative analysis of deeply phenotyped GBM cohorts of ‘short-term’ and ‘long-term’ survivors |
title_short | Comparative analysis of deeply phenotyped GBM cohorts of ‘short-term’ and ‘long-term’ survivors |
title_sort | comparative analysis of deeply phenotyped gbm cohorts of ‘short-term’ and ‘long-term’ survivors |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322749/ https://www.ncbi.nlm.nih.gov/pubmed/37237151 http://dx.doi.org/10.1007/s11060-023-04341-3 |
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