Abstract
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.
Highlights
Glioblastoma (GBM) is the most frequent primary malignant brain tumor and is one of the most aggressive neoplasms among the human cancers [1]
We show that PATZ1 suppresses the expression of the mesenchyme-inducer CXCR4, and that PATZ1 and CXCR4 are inversely correlated in glioma-initiating stem cells (GSCs) and proneural GBM
Using paraffin embedded sections generated from surgical specimens collected at the Department of Advanced Biomedical Sciences, Pathology Section, of the University of Naples Federico II, we analysed by immunohistochemistry PATZ1 expression in 45 grade IV GBM, 22 oligodendrogliomas (10 grade III and 12 grade II) and 26 perilesional normal brain parenchymas
Summary
Glioblastoma (GBM) is the most frequent primary malignant brain tumor and is one of the most aggressive neoplasms among the human cancers [1]. It is characterized by dismal prognosis with median survival of 16–19 months despite multimodal treatment including surgical resection followed by combined radiochemotherapy [2]. In spite of enormous efforts towards understanding the molecular basis of the disease and the development of novel therapeutic strategies, only limited advances have been achieved and there is a pressing need to identify proteins and signalling pathways that can serve as new targets for an improved treatment of GBM. Therapeutic targets in glioma-initiating stem cells (GSCc) are a focus of increasing interest to improve the GBM outcome
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