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PROX1 is a novel pa...
PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status
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- Roodakker, Kenney R. (author)
- Uppsala universitet,Neurologi,Uppsala University, Sweden
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- Elsir, Tamador (author)
- Karolinska Institutet,Uppsala universitet,Neurologi,Karolinska Inst, Karolinska Univ Hosp, Dept Oncol Pathol, Canc Ctr Karolinska R8 05, Stockholm, Sweden,Uppsala University, Sweden; Karolinska Institute, Sweden
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- Edqvist, Per-Henrik D (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden
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- Hagerstrand, D. (author)
- Karolinska Institutet
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- Carison, J. (author)
- Karolinska Inst, Karolinska Univ Hosp, Dept Oncol Pathol, Canc Ctr Karolinska R8 05, Stockholm, Sweden,Karolinska Institute, Sweden
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- Lysiak, Malgorzata (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Henriksson, Roger (author)
- Umeå universitet,Onkologi,Regional Cancer Center, Stockholm Gotland, Stockholm, Sweden,Umea Univ, Dept Radiat Sci & Oncol, Umea, Sweden.; Reg Canc Ctr, Stockholm, Sweden,Umeå University, Sweden; Regional Cancer Centre, Sweden
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- Pontén, Fredrik (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden
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- Rosell, Johan (author)
- Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Region Östergötland, Regionalt cancercentrum
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- Söderkvist, Peter (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi och klinisk genetik
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- Stupp, R. (author)
- Univ Zurich Hosp, Dept Oncol, Zurich, Switzerland,University of Zurich Hospital, Switzerland
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- Tchougounova, Elena (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala University, Sweden
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- Nister, M. (author)
- Karolinska Institutet
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- Malmström, Annika (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, LAH Linköping
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- Smits, Anja (author)
- Uppsala universitet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för hälsa och rehabilitering,Institute of Neuroscience and Physiology, Department of Health and Rehabilitation,Neurologi,Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci & Rehabil, Inst Neurosci & Physiol, Gothenburg, Sweden,Uppsala University, Sweden; University of Gothenburg, Sweden
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(creator_code:org_t)
- 2016-09-10
- 2016
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:45, s. 72431-72442
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- PROX1
- malignant astrocytomas
- IDH mutations
- primary glioblastomas
- secondary glioblastomas
- Gerotarget
- central-nervous-system
- gliomas
- survival
- tumors
- brain
- cells
- classification
- radiotherapy
- temozolomide
- population
- Oncology
- Cell Biology
- PROX1
Publication and Content Type
- ref (subject category)
- art (subject category)
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Roodakker, Kenne ...
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Elsir, Tamador
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Edqvist, Per-Hen ...
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Hagerstrand, D.
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Carison, J.
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Lysiak, Malgorza ...
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Henriksson, Roge ...
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Pontén, Fredrik
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Rosell, Johan
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Söderkvist, Pete ...
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Stupp, R.
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Tchougounova, El ...
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Nister, M.
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Malmström, Annik ...
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Smits, Anja
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Oncotarget
- By the university
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University of Gothenburg
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Umeå University
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Uppsala University
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Linköping University
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Karolinska Institutet