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...
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| Veröffentlicht in: | JOURNAL OF NEURO-ONCOLOGY 2023-06, Vol.163 (2), p.327-338 |
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| creator | Biswas, Archita Salvucci, Manuela Connor, Kate Dussmann, 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 |
| 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 |
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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.</description><identifier>ISSN: 0167-594X</identifier><language>eng</language><publisher>SPRINGER</publisher><ispartof>JOURNAL OF NEURO-ONCOLOGY, 2023-06, Vol.163 (2), p.327-338</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,776,780,27837</link.rule.ids></links><search><creatorcontrib>Biswas, Archita</creatorcontrib><creatorcontrib>Salvucci, Manuela</creatorcontrib><creatorcontrib>Connor, Kate</creatorcontrib><creatorcontrib>Dussmann, Heiko</creatorcontrib><creatorcontrib>Carberry, Steven</creatorcontrib><creatorcontrib>Fichtner, Michael</creatorcontrib><creatorcontrib>King, Ellen</creatorcontrib><creatorcontrib>Murphy, Brona</creatorcontrib><creatorcontrib>O'Farrell, Alice C</creatorcontrib><creatorcontrib>Cryan, Jane</creatorcontrib><creatorcontrib>Beausang, Alan</creatorcontrib><creatorcontrib>Heffernan, Josephine</creatorcontrib><creatorcontrib>Cremona, Mattia</creatorcontrib><creatorcontrib>Hennessy, Bryan T</creatorcontrib><creatorcontrib>Clerkin, James</creatorcontrib><creatorcontrib>Sweeney, Kieron J</creatorcontrib><creatorcontrib>MacNally, Steve</creatorcontrib><creatorcontrib>Brett, Francesca</creatorcontrib><creatorcontrib>O'Halloran, Philip</creatorcontrib><creatorcontrib>Bacon, Orna</creatorcontrib><creatorcontrib>Furney, Simon</creatorcontrib><creatorcontrib>Verreault, Maite</creatorcontrib><creatorcontrib>Quissac, Emie</creatorcontrib><creatorcontrib>Bielle, Franck</creatorcontrib><creatorcontrib>Ahmed, Mohammed H</creatorcontrib><creatorcontrib>Idbaih, Ahmed</creatorcontrib><creatorcontrib>Leenstra, Sieger</creatorcontrib><creatorcontrib>Ntafoulis, Ioannis</creatorcontrib><creatorcontrib>Fabro, Federica</creatorcontrib><creatorcontrib>Lamfers, Martine</creatorcontrib><creatorcontrib>Golebiewska, Anna</creatorcontrib><creatorcontrib>Hertel, Frank</creatorcontrib><creatorcontrib>Niclou, Simone P</creatorcontrib><creatorcontrib>Yen, Romain Tching Chi</creatorcontrib><creatorcontrib>Kremer, Andreas</creatorcontrib><creatorcontrib>Dilcan, Gonca</creatorcontrib><creatorcontrib>Lodi, Francesca</creatorcontrib><creatorcontrib>Arijs, Ingrid</creatorcontrib><creatorcontrib>Lambrechts, Diether</creatorcontrib><creatorcontrib>Purushothama, Manasa Kalya</creatorcontrib><creatorcontrib>Kel, Alexander</creatorcontrib><creatorcontrib>Byrne, Annette T</creatorcontrib><creatorcontrib>Prehn, Jochen H.M</creatorcontrib><title>Comparative analysis of deeply phenotyped GBM cohorts of 'short-term' and 'long-term' survivors</title><title>JOURNAL OF NEURO-ONCOLOGY</title><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.</description><issn>0167-594X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>FZOIL</sourceid><recordid>eNqVjMkOgjAURbvQRBz-oTsSE0yZJGwlDht3Ltw1DTwELbTpK0T-3iF8gK7uucm5d0Ic5m8TL06j64zMEe-MsSgJfYfwTDVaGGHrHqhohRywRqpKWgBoOVBdQavsoKGgx92Z5qpSxn4FFz_oWTCN-14W1JWqvY0dO9PXvTK4JNNSSITVmAuyPuwv2cl7dBK6HlpeoBY58IDxmDHuB2kU8CRgSRqGC7L5Web2acO_3l-881Ty</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Biswas, Archita</creator><creator>Salvucci, Manuela</creator><creator>Connor, Kate</creator><creator>Dussmann, Heiko</creator><creator>Carberry, Steven</creator><creator>Fichtner, Michael</creator><creator>King, Ellen</creator><creator>Murphy, Brona</creator><creator>O'Farrell, Alice C</creator><creator>Cryan, Jane</creator><creator>Beausang, Alan</creator><creator>Heffernan, Josephine</creator><creator>Cremona, Mattia</creator><creator>Hennessy, Bryan T</creator><creator>Clerkin, James</creator><creator>Sweeney, Kieron J</creator><creator>MacNally, Steve</creator><creator>Brett, Francesca</creator><creator>O'Halloran, Philip</creator><creator>Bacon, Orna</creator><creator>Furney, Simon</creator><creator>Verreault, Maite</creator><creator>Quissac, Emie</creator><creator>Bielle, Franck</creator><creator>Ahmed, Mohammed H</creator><creator>Idbaih, Ahmed</creator><creator>Leenstra, Sieger</creator><creator>Ntafoulis, Ioannis</creator><creator>Fabro, Federica</creator><creator>Lamfers, Martine</creator><creator>Golebiewska, Anna</creator><creator>Hertel, Frank</creator><creator>Niclou, Simone P</creator><creator>Yen, Romain Tching Chi</creator><creator>Kremer, Andreas</creator><creator>Dilcan, Gonca</creator><creator>Lodi, Francesca</creator><creator>Arijs, Ingrid</creator><creator>Lambrechts, Diether</creator><creator>Purushothama, Manasa Kalya</creator><creator>Kel, Alexander</creator><creator>Byrne, Annette T</creator><creator>Prehn, Jochen H.M</creator><general>SPRINGER</general><scope>FZOIL</scope></search><sort><creationdate>202306</creationdate><title>Comparative analysis of deeply phenotyped GBM cohorts of 'short-term' and 'long-term' survivors</title><author>Biswas, Archita ; 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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.</abstract><pub>SPRINGER</pub><oa>free_for_read</oa></addata></record> |
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| title | Comparative analysis of deeply phenotyped GBM cohorts of 'short-term' and 'long-term' survivors |
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