PATZ1 is a new prognostic marker of glioblastoma associated with the stem-like phenotype and enriched in the proneural subtype
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Elia Guadagno1, Michela Vitiello2, Paola Francesca2, Gaetano Calì2, Federica Caponnetto3, Daniela Cesselli3, Simona Camorani2, Giorgio Borrelli1, Marialuisa Califano1, Paolo Cappabianca4, Claudio Arra5, Elvira Crescenzi2, Laura Cerchia2, Maria Laura Del Basso De Caro1 and Monica Fedele2
1Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, 80131 Naples, Italy
2Institute of Experimental Endocrinology and Oncology (IEOS) “Gaetano Salvatore”, National Council of Research, 80131 Naples, Italy
3Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
4Division of Neurosurgery, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy
5Department of Experimental Oncology, National Cancer Institute “Fondazione Giovanni Pascale”, IRCCS, 80131 Naples, Italy
Maria Laura Del Basso De Caro, email: email@example.com
Keywords: glioma, glioma stem cells, PATZ1, tumor heterogeneity, biomarker
Received: January 18, 2017 Accepted: June 19, 2017 Published: July 25, 2017
Glioblastoma (GBM), the most malignant of the brain tumors, has been classified on the basis of molecular signature into four subtypes: classical, mesenchymal, proneural and neural, among which the mesenchymal and proneural subtypes have the shortest and longest survival, respectively. Here we show that the transcription factor PATZ1 gene is upregulated in gliomas compared to normal brain and, among GBMs, is particularly enriched in the proneural subtype and co-localize with stemness markers. Accordingly, in GBM-derived glioma-initiating stem cells (GSCs) PATZ1 is overexpressed compared to differentiated tumor cells and its expression significantly correlates with the characteristic stem cell capacity to grow as neurospheres in vitro. Interestingly, survival analysis demonstrated that PATZ1 lower levels informed poor prognosis in GBM and, specifically, in the proneural subgroup, suggesting it may serve a role as diagnostic and prognostic biomarker for intra-subtype heterogeneity of proneural GBM. We also show that PATZ1 suppresses the expression of the mesenchyme-inducer CXCR4, and that PATZ1 and CXCR4 are inversely correlated in GSC and proneural GBM. Overall these findings support a central role of PATZ1 in regulating malignancy of GBM.
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