STAT5b is a marker of poor prognosis, rather than a therapeutic target in glioblastomas

Dubois,Nadège; Berendsen,Sharon; Tan,Katherine; Schoysmans,Laurent; Spliet,Wim; Seute,Tatjana; Bours,Vincent; Robe,Pierre A.

doi:10.3892/ijo.2022.5414

STAT5b is a marker of poor prognosis, rather than a therapeutic target in glioblastomas

Authors:
- Nadège Dubois
- Sharon Berendsen
- Katherine Tan
- Laurent Schoysmans
- Wim Spliet
- Tatjana Seute
- Vincent Bours
- Pierre A. Robe
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Affiliations: Department of Neurology and Neurosurgery, and The T&P Bohnenn Laboratory for Neuro‑Oncology, University Medical Center of Utrecht, 3584CX Utrecht, The Netherlands, Department of Radiology, University Medical Center of Liège, 4000 Liege, Belgium, Department of Pathology, University Medical Center of Utrecht, 3584CX Utrecht, The Netherlands, Human Genetics Laboratory, GIGA‑Cancer Center, University of Liège, 4000 Liege, Belgium
Published online on: September 5, 2022 https://doi.org/10.3892/ijo.2022.5414
Article Number: 124
Copyright: © Dubois et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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