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

被引：5

作者：

Biswas, Archita ^{[1
]}

Salvucci, Manuela ^{[1
]}

Connor, Kate ^{[1
]}

Dussmann, Heiko ^{[1
]}

Carberry, Steven ^{[1
]}

Fichtner, Michael ^{[1
]}

King, Ellen ^{[1
]}

Murphy, Brona ^{[1
]}

O'Farrell, Alice C. ^{[1
]}

Cryan, Jane ^{[2
]}

Beausang, Alan ^{[2
]}

Heffernan, Josephine ^{[2
]}

Cremona, Mattia ^{[3
,4
]}

Hennessy, Bryan T. ^{[3
,4
]}

Clerkin, James ^{[1
,5
]}

Sweeney, Kieron J. ^{[5
]}

MacNally, Steve ^{[5
]}

Brett, Francesca ^{[2
]}

O'Halloran, Philip ^{[5
]}

Bacon, Orna ^{[1
]}

Furney, Simon ^{[1
]}

Verreault, Maite ^{[6
]}

Quissac, Emie ^{[6
]}

Bielle, Franck ^{[6
]}

Ahmed, Mohammed H. ^{[6
]}

Idbaih, Ahmed ^{[6
]}

Leenstra, Sieger ^{[7
]}

Ntafoulis, Ioannis ^{[7
]}

Fabro, Federica ^{[7
]}

Lamfers, Martine ^{[7
]}

Golebiewska, Anna ^{[8
]}

Hertel, Frank ^{[8
,12
]}

Niclou, Simone P. ^{[8
,12
]}

Yen, Romain Tching Chi ^{[9
]}

Kremer, Andreas ^{[9
]}

Dilcan, Gonca ^{[10
]}

Lodi, Francesca ^{[10
]}

Arijs, Ingrid ^{[10
]}

Lambrechts, Diether ^{[10
]}

Purushothama, Manasa Kalya ^{[11
]}

Kel, Alexander ^{[11
]}

Byrne, Annette T. ^{[1
]}

Prehn, Jochen H. M. ^{[1
]}

机构：

[1] Royal Coll Surgeons Ireland, Ctr Syst Med, Dept Physiol & Med Phys, 123 St Stephens Green, Dublin D02 YN77 2, Ireland

[2] Beaumont Hosp, Dept Neuropathol, Dublin 9, Ireland

[3] Royal Coll Surgeons Ireland, Dept Med, Dublin 9, Ireland

[4] Beaumont Hosp, Dublin 9, Ireland

[5] Beaumont Hosp, Dept Neurosurg, Dublin 9, Ireland

[6] Sorbonne Univ, Hop Univ La Pitie Salpetriere Charles Foix, AP HP,ICM,Inserm, Inst Cerveau,Paris Brain Inst,DMU Neurosci,CNRS, F-75013 Paris, France

[7] Erasmus Univ, Dept Neurosurg, Brain Tumor Ctr, Med Ctr, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands

[8] Luxembourg Inst Hlth, Dept Canc Res, NORLUX Neurooncol Lab, 6A,Rue Nicolas Ernest Barble, L-1210 Luxembourg, Luxembourg

[9] Informat Technol Translat Med, 27 Rue Henri Koch House Biohlth, L-4354 Esch Sur Alzette, Luxembourg

[10] Katholieke Univ Leuven, Canc Canc Biol, VIB, Onderwijs Navorsing 5,Herestr 49, B-3000 Leuven, Belgium

[11] GeneXplain GmbH, Am Exer 19b, D-38302 Wolfenbuttel, Germany

[12] Univ Luxembourg, Fac Sci Technol & Med, L-4365 Esch Sur Alzette, Luxembourg

来源：

JOURNAL OF NEURO-ONCOLOGY | 2023年 / 163卷 / 02期

关键词：

Glioblastoma; Reverse phase protein array; RNA-sequencing; Transcriptomics; Cilium; Cell cycle; Apoptosis; Short term survivors; Long term survivors; TUMOR MICROENVIRONMENT; EXPRESSION; IDENTIFICATION; PROGNOSIS; EVOLUTION; HYPOXIA; PATHWAY; GROWTH; ROLES;

D O I：

10.1007/s11060-023-04341-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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; Stuppprotocol as first line treatment, IDH wild type), and a multiomic 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 expres-sion 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.

引用

页码：327 / 338

页数：12

共 40 条

[1] FAK Inhibition Induces Glioblastoma Cell Senescence-Like State through p62 and p27 [J].

Alza, Lia ;

Nager, Mireia ;

Visa, Anna ;

Canti, Carles ;

Herreros, Judit .

CANCERS, 2020, 12 (05)

[2]

Boellner Stefanie, 2015, Microarrays (Basel), V4, P98, DOI 10.3390/microarrays4020098

[3] TRANSPATH® -: a high quality database focused on signal transduction [J].

Choi, C ;

Krull, M ;

Kel, A ;

Kel-Margoulis, O ;

Pistor, S ;

Potapov, A ;

Voss, N ;

Wingender, E .

COMPARATIVE AND FUNCTIONAL GENOMICS, 2004, 5 (02) :163-168

[4] Shaping Up the Tumor Microenvironment With Cellular Fibronectin [J].

Efthymiou, Georgios ;

Saint, Angelique ;

Ruff, Michael ;

Rekad, Zeinab ;

Ciais, Delphine ;

Van Obberghen-Schilling, Ellen .

FRONTIERS IN ONCOLOGY, 2020, 10

[5] Integrin Signaling in Glioma Pathogenesis: From Biology to Therapy [J].

Ellert-Miklaszewska, Aleksandra ;

Poleszak, Katarzyna ;

Pasierbinska, Maria ;

Kaminska, Bozena .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (03)

[6] A preclinical evaluation of the PI3K alpha/delta dominant inhibitor BAY 80-6946 in HER2-positive breast cancer models with acquired resistance to the HER2-targeted therapies trastuzumab and lapatinib [J].

Elster, N. ;

Cremona, M. ;

Morgan, C. ;

Toomey, S. ;

Carr, A. ;

O'Grady, A. ;

Hennessy, B. T. ;

Eustace, A. J. .

BREAST CANCER RESEARCH AND TREATMENT, 2015, 149 (02) :373-383

[7] Presence of primary cilia in cancer cells correlates with prognosis of pancreatic ductal adenocarcinoma [J].

Emoto, Katsura ;

Masugi, Yohei ;

Yamazaki, Ken ;

Effendi, Kathryn ;

Tsujikawa, Hanako ;

Tanabe, Minoru ;

Kitagawa, Yuko ;

Sakamoto, Michiie .

HUMAN PATHOLOGY, 2014, 45 (04) :817-825

[8] Profiling Anti-Apoptotic BCL-xL Protein Expression in Glioblastoma Tumorspheres [J].

Fanfone, Deborah ;

Idbaih, Ahmed ;

Mammi, Jade ;

Gabut, Mathieu ;

Ichim, Gabriel .

CANCERS, 2020, 12 (10) :1-14

[9] Surgery for Glioblastoma in Light of Molecular Markers: Impact of Resection and MGMT Promoter Methylation in Newly Diagnosed IDH-1 Wild-Type Glioblastomas [J].

Gessler, Florian ;

Bernstock, Joshua D. ;

Braczynski, Anne ;

Lescher, Stephanie ;

Baumgarten, Peter ;

Harter, Patrick N. ;

Mittelbronn, Michel ;

Wu, Tianxia ;

Seifert, Volker ;

Senft, Christian .

NEUROSURGERY, 2019, 84 (01) :190-197

[10] MGMT gene silencing and benefit from temozolomide in glioblastoma [J].

Hegi, ME ;

Diserens, A ;

Gorlia, T ;

Hamou, M ;

de Tribolet, N ;

Weller, M ;

Kros, JM ;

Hainfellner, JA ;

Mason, W ;

Mariani, L ;

Bromberg, JEC ;

Hau, P ;

Mirimanoff, RO ;

Cairncross, JG ;

Janzer, RC ;

Stupp, R .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (10) :997-1003

← 1 2 3 4 →