PARP1 expression and its correlation with survival is tumour molecular subtype dependent in glioblastoma
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Balázs Murnyák1, Mahan C. Kouhsari1, Rotem Hershkovitch1, Bernadette Kálmán2,3, György Marko-Varga4, Álmos Klekner5 and Tibor Hortobágyi1,6
1Division of Neuropathology, Institute of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
2Institute of Diagnostics, Faculty of the Health Sciences, University of Pecs, Pecs, Hungary
3Molecular Pathology Unit, Markusovszky Teaching Hospital, Szombathely, Hungary
4Division of Clinical Protein Science & Imaging, Department of Biomedical Engineering, Lund University, Lund, Sweden
5Department of Neurosurgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
6Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
Tibor Hortobágyi, email: [email protected], [email protected]
Keywords: glioma, glioblastoma, p53, PARP1
Received: December 27, 2016 Accepted: April 24, 2017 Published: May 19, 2017
Overexpression of PARP1 exists in various cancers, including glioblastoma (GBM). Although PARP1 inhibition is a promising therapeutic target, no comprehensive study has addressed PARP1’s expression characteristics and prognostic role regarding molecular heterogeneity in astrocytomas including GBM. Our aim was to evaluate PARP1’s associations with survival, WHO grade, lineage specific markers, and GBM transcriptomic subtypes. We collected genomic and clinical data from the latest glioma datasets of The Cancer Genome Atlas and performed PARP1, ATRX, IDH1, and p53 immunohistochemistry on GBM tissue samples. We demonstrated that PARP1 gain and increased mRNA expression are characteristics of high-grade astrocytomas, particularly of Proneural and Classical GBM subtypes. Additionally, higher PARP1 levels exhibited an inverse correlation with patient survival (p<0.005) in the Classical subgroup. ATRX (p=0.006), and TP53 (p=0.015) mutations were associated with increased PARP1 expression and PARP1 protein level correlated with ATRX loss and p53 overexpression. Furthermore, higher PARP1 expression together with wildtype TP53 indicated shorter survival (p=0.039). Therefore, due to subtype specificity, PARP1 expression level and TP53 mutation status are reliable marker candidates to distinguish Proneural and Classical subtypes, with prognostic and therapeutic implications in GBM.
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