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Expression and prognostic value of the WEE1 kinase in gliomas

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Abstract

High-grade gliomas have an aggressive clinical course and new clinical biomarkers and therapeutic targets are highly needed. WEE1 is a regulator of the G2 checkpoint in glioblastoma (GBM) cells. Inhibition of this kinase has, in experimental glioma studies, been suggested to enhance sensitivity to irradiation and temozolomide. However, expression level and prognostic potential of WEE1 protein in gliomas remain uninvestigated. In this study, glioma samples from 235 patients across all four WHO grades were analyzed by immunohistochemistry. Using image analysis, we calculated the area fraction of WEE1 positive nuclei. We found that WEE1 protein was localized in tumor cell nuclei and expressed in all glioma types and grades. Although WEE1 protein levels are higher in GBMs (mean 24.5 %) relative to grade III (mean 14,0 %, p < 0.05) and grade II (mean 6.8 %, p < 0.001) gliomas, high WEE1 protein was associated with better survival in GBMs (p = 0.002). This was confirmed in multivariate analysis (HR 0.60, p = 0.003) even when adjusted for MGMT status (HR 0.60, p = 0.005). In conclusion, we report a nuclear expression of WEE1 protein in all glioma grades and types. The WEE1 positive nuclear area was correlated with malignancy grade but it was inversely associated with prognosis in GBM. Although WEE1 is a frequently occurring protein and has been proposed as a novel target in GBM, the role of WEE1 in glioma patient survival appears to be connected to the MGMT status and is more complex than previously anticipated.

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Acknowledgments

We acknowledge the excellent laboratory work performed by technicians Helle Wohlleben and Tanja Dreehsen Højgaard.

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Authors and Affiliations

  1. Department of Pathology, Odense University Hospital, J. B. Winsløws Vej 15, Odense C, Denmark

    Darija Music, Rikke Hedegaard Dahlrot, Simon Kjær Hermansen, Karin de Stricker & Bjarne Winther Kristensen

  2. Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, Odense C, Denmark

    Rikke Hedegaard Dahlrot & Steinbjørn Hansen

  3. Institute of Clinical Research, University of Southern Denmark, Winsløwparken 19, Odense C, Denmark

    Simon Kjær Hermansen, Steinbjørn Hansen & Bjarne Winther Kristensen

  4. Department of Epidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 9, Odense C, Denmark

    Jacob Hjelmborg

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  1. Darija Music
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  2. Rikke Hedegaard Dahlrot
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  3. Simon Kjær Hermansen
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  7. Bjarne Winther Kristensen
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Correspondence to Bjarne Winther Kristensen.

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Music, D., Dahlrot, R.H., Hermansen, S.K. et al. Expression and prognostic value of the WEE1 kinase in gliomas. J Neurooncol 127, 381–389 (2016). https://doi.org/10.1007/s11060-015-2050-4

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  • DOI: https://doi.org/10.1007/s11060-015-2050-4

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