PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status

Kenney R. Roodakker*, Tamador Elsir, Per Henrik D Edqvist, Daniel Hägerstrand, Joseph Carlson, Malgorzata Lysiak, Roger Henriksson, Fredrik Pontén, Johan Rosell, Peter Söderkvist, Roger Stupp, Elena Tchougounova, Monica Nistér, Annika Malmström, Anja Smits

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)72431-72442
Number of pages12
JournalOncotarget
Volume7
Issue number45
DOIs
StatePublished - 2016

Keywords

  • Gerotarget
  • IDH mutations
  • Malignant astrocytomas
  • PROX1
  • Primary glioblastomas
  • Secondary glioblastomas

ASJC Scopus subject areas

  • Oncology

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    Roodakker, K. R., Elsir, T., Edqvist, P. H. D., Hägerstrand, D., Carlson, J., Lysiak, M., Henriksson, R., Pontén, F., Rosell, J., Söderkvist, P., Stupp, R., Tchougounova, E., Nistér, M., Malmström, A., & Smits, A. (2016). PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status. Oncotarget, 7(45), 72431-72442. https://doi.org/10.18632/oncotarget.11957