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PROX1 is a predictor of survival for gliomas WHO grade II
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. (Neurologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. (Neurologi)
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2011 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, no 11, 1747-1754 p.Article in journal (Refereed) Published
Abstract [en]

Background:The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcription factor that has a critical role in the development of various organs. PROX1 has been ascribed both oncogenic and tumour suppressive functions in human cancers. We have recently shown that PROX1 may act as a diagnostic marker for high-grade gliomas. The aim of this study was to address the prognostic value of PROX1 in grade II gliomas.Methods:A total of 116 samples were evaluated for the presence of PROX1 protein. The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.Results:Higher PROX1 protein was associated with poor outcome. In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.Conclusion:PROX1 is a novel predictor of survival for grade II gliomas.

Place, publisher, year, edition, pages
2011. Vol. 104, no 11, 1747-1754 p.
Keyword [en]
low-grade glioma, astrocytoma, oligodendroglioma, PROX1, prognosis, survival
National Category
Neurology
Research subject
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-154452DOI: 10.1038/bjc.2011.162ISI: 000290953200014PubMedID: 21559010OAI: oai:DiVA.org:uu-154452DiVA: diva2:420505
Available from: 2011-06-01 Created: 2011-06-01 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Towards Novel Biomarkers for Low-grade Glioma
Open this publication in new window or tab >>Towards Novel Biomarkers for Low-grade Glioma
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gliomas are common primary brain tumours that occur as low-grade (LGG) and high-grade gliomas (HGG). Typically occurring in younger adults, LGG has an indolent course with a median survival of 5-10 years, but carries an inherent potential for transforming into HGG. The thesis focused on LGG in adults, with the aim of identifying prognostic biomarkers for LGG.

Paper I. Epileptic seizures are common symptoms in LGG. In a retrospective study, the correlation between 11C-methionine (MET) uptake, measured by Positron Emission Tomography (PET), and seizure activity was assessed in 101 patients with LGG. Although there was no correlation between MET uptake and seizure activity, survival was longer in patients who were seizure-free before surgery.

Paper II. This finding prompted the search for common genetic pathways for both tumour and seizure development and a review of genetic polymorphisms in focal epilepsy and glioma risk. Cell cycle and immune response genes affecting both glioma and seizure risk were identified, and genes involved in synaptic transmission presented potential candidates for future studies.

Paper III. The transcription factor PROX1 plays a pivotal role in normal development and carcinogenesis of various organs. The prognostic value of PROX1, together with established clinical and molecular prognostic factors for survival, was retrospectively assessed in 116 patients with LGG. High PROX1 expression in the tumour was associated with shorter survival.

Paper IV. DNA repair enzymes, such as ERCC6, are crucial for maintaining genomic stability in glioma response to radiotherapy. An association between the polymorphism rs4253079, mapped to ERCC6, and longer survival in patients with LGG and HGG was identified.

Paper V. As LGG typically presented as non-contrast enhancing tumours on morphological MRI (magnetic resonance imaging), the value of combined MET PET with physiological MRI for preoperative diagnosis was assessed in a prospective study of 32 patients with suspected LGG. Representative tumour areas were identified through a combination of perfusion-MRI with MET PET, which can be used as a baseline investigation for follow-up over time.

Conclusions: The parameters seizure-freedom before surgery, the polymorphism rs4253079 in ERCC6 and low PROX1 expression in the tumor were identified as favorable prognostic biomarkers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 834
Keyword
Low-grade glioma, prognosis, epilepsy, PROX1, DNA repair enzyme, PET, Physiological MRI
National Category
Medical and Health Sciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-183363 (URN)978-91-554-8518-4 (ISBN)
Public defence
2012-12-10, Rosénsalen, Akademiska sjukhuset, ing. 95, Uppsala, 13:00 (Swedish)
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Available from: 2012-11-19 Created: 2012-10-24 Last updated: 2013-01-23Bibliographically approved

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Berntsson, Shala G.Smits, Anja

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