Article (Scientific journals)
STAT5b is a marker of poor prognosis, rather than a therapeutic target in glioblastomas.
Dubois, Nadège; Berendsen, Sharon; Tan, Katherine et al.
2022In International Journal of Oncology, 61 (4)
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Keywords :
STAT5b; glioblastoma; Prognosis; Brain Neoplasms/drug therapy; Brain Neoplasms/genetics; Glioblastoma/genetics; Brain Neoplasms; Oncology; Cancer Research
Abstract :
[en] The copy number and mRNA expression of STAT5b were assessed in samples from the TCGA repository of glioblastomas (GBM). The activation of this transcription factor was analyzed on tissue microarrays comprising 392 WHO 2016 GBM samples from our clinical practice. These data were correlated with patient survival using multivariable Cox analysis and, for a subset of 167 tumors, with signs of tumor invasiveness on the MRI. The effects of STAT5b knockdown by siRNA were assessed on the growth, therapeutic resistance, invasion and migration of GBM cell lines U87, U87‑EGFRVIII and LN18 and primary cultures GM2 and GM3. The activation, but not the copy number or the mRNA expression of nuclear transcription factor STAT5b expression correlated inversely with patient survival independently of IDH1R132H status, age, Karnofsky Performance Score, treatment and tumor volume. STAT5b inhibition neither altered the cell proliferation nor reduced the clonogenic proliferative potency of GBM cells, and did not sensitize them to the cytotoxic effect of ionizing radiation and temozolomide in vitro. STAT5b inhibition significantly increased GBM cell migration, but decreased the invasion of some GBM cells in vitro. There was no correlation between the activation of STAT5b in clinical tumors and the extent of invasion on MRI OF patients. In conclusion, STAT5b is frequently activated in GBM and correlates inversely with patient survival. It does not contribute to the growth and resistance of these tumors, and is thus rather a potential prognostic marker than a therapeutic target in these tumors.
Disciplines :
Oncology
Author, co-author :
Dubois, Nadège  ;  Centre Hospitalier Universitaire de Liège - CHU > > Faculté de médecine ; Department of Neurology and Neurosurgery, and The T&P Bohnenn Laboratory for Neuro‑Oncology, University Medical Center of Utrecht, 3584CX Utrecht, The Netherlands
Berendsen, Sharon;  Department of Neurology and Neurosurgery, and The T&P Bohnenn Laboratory for Neuro‑Oncology, University Medical Center of Utrecht, 3584CX Utrecht, The Netherlands
Tan, Katherine;  Department of Neurology and Neurosurgery, and The T&P Bohnenn Laboratory for Neuro‑Oncology, University Medical Center of Utrecht, 3584CX Utrecht, The Netherlands
Schoysmans, Laurent;  Department of Radiology, University Medical Center of Liège, 4000 Liege, Belgium
Spliet, Wim;  Department of Pathology, University Medical Center of Utrecht, 3584CX Utrecht, The Netherlands
Seute, Tatjana;  Department of Neurology and Neurosurgery, and The T&P Bohnenn Laboratory for Neuro‑Oncology, University Medical Center of Utrecht, 3584CX Utrecht, The Netherlands
Bours, Vincent ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Robe, Pierre ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique humaine ; Department of Neurology and Neurosurgery, and The T&P Bohnenn Laboratory for Neuro‑Oncology, University Medical Center of Utrecht, 3584CX Utrecht, The Netherlands
Language :
English
Title :
STAT5b is a marker of poor prognosis, rather than a therapeutic target in glioblastomas.
Publication date :
October 2022
Journal title :
International Journal of Oncology
ISSN :
1019-6439
eISSN :
1791-2423
Publisher :
NLM (Medline), Greece
Volume :
61
Issue :
4
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 26 September 2022

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