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PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Karolinska Inst, Karolinska Univ Hosp, Dept Oncol Pathol, Canc Ctr Karolinska R8 05, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Karolinska Inst, Karolinska Univ Hosp, Dept Oncol Pathol, Canc Ctr Karolinska R8 05, Stockholm, Sweden.
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 45, 72431-72442 p.Article in journal (Refereed) Published
Abstract [en]

PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma. Representing the younger population of glioblastomas, we studied 80 IDH-wildtype glioblastomas from patients aged 18-60 years. There was no correlation between PROX1 protein and survival for patients with primary glioblastomas included in these cohorts. In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas. The prognostic impact of PROX1 in IDH-mutant 1p19q non-codeleted high-grade astrocytomas, as well as the negative findings in primary glioblastomas, was corroborated by gene expression data extracted from the Cancer Genome Atlas. We conclude that PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing low-grade tumors and harbor IDH mutations.

Place, publisher, year, edition, pages
2016. Vol. 7, no 45, 72431-72442 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-303717DOI: 10.18632/oncotarget.11957ISI: 000387452100004PubMedID: 27626492OAI: oai:DiVA.org:uu-303717DiVA: diva2:973835
Funder
The King Gustaf V's Jubilee FoundationSwedish Cancer SocietyThe Karolinska Institutet's Research Foundation
Available from: 2016-09-22 Created: 2016-09-22 Last updated: 2017-11-21Bibliographically approved

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Roodakker, Kenney R.Edqvist, Per-Henrik DPontén, FredrikSmits, Anja
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