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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, Sweden.
Uppsala University, Sweden; Karolinska Institute, Sweden.
Uppsala University, Sweden.
Karolinska Institute, Sweden.
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 45, p. 72431-72442Article 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 lowgrade tumors and harbor IDH mutations.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC , 2016. Vol. 7, no 45, p. 72431-72442
Keywords [en]
PROX1; malignant astrocytomas; IDH mutations; primary glioblastomas; secondary glioblastomas; Gerotarget
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-132988DOI: 10.18632/oncotarget.11957ISI: 000387452100004PubMedID: 27626492OAI: oai:DiVA.org:liu-132988DiVA, id: diva2:1054738
Note

Funding Agencies|Erik, Karin och Gosta Selanders Fund; Uppsala County Council; Hanna Eklund Fund; King Gustaf V Jubilee Fund, Stockholm; Swedish Cancer Society; Swedish Research Council; VR-Linne (STARGET); Karolinska Institutet; Karolinska University Hospital/Stockholm County Council; Lions Cancer Research Foundation; University of Umea; Merck; Ostergotland County Council for Clinical Neuroscience Research

Available from: 2016-12-09 Created: 2016-12-07 Last updated: 2018-05-02

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Lysiak, MalgorzataRosell, JohanSöderkvist, PeterMalmström, Annika
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Division of Cell BiologyFaculty of Medicine and Health SciencesDivision of Clinical SciencesRegional Cancer Center South East SwedenDepartment of Clinical Pathology and Clinical GeneticsDepartment of Advanced Home Care in Linköping
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