Guadagno, Elia (2017) Prognostic role of PATZ1 protein in gliomas and its implication with stemness. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Prognostic role of PATZ1 protein in gliomas and its implication with stemness
Creators:
CreatorsEmail
Guadagno, Eliaeliaguadagno84@gmail.com
Date: 20 September 2017
Number of Pages: 69
Institution: Università degli Studi di Napoli Federico II
Department: dep18
Dottorato: phd076
Ciclo di dottorato: 30
Coordinatore del Corso di dottorato:
nomeemail
Cuocolo, Albertocuocolo@unina.it
Tutor:
nomeemail
De Rosa, GaetanoUNSPECIFIED
Date: 20 September 2017
Number of Pages: 69
Uncontrolled Keywords: glioblastoma, PATZ1, proneural
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/08 - Anatomia patologica
Date Deposited: 18 Dec 2017 12:29
Last Modified: 22 Mar 2019 10:11
URI: http://www.fedoa.unina.it/id/eprint/12157

Abstract

Glioblastoma (GBM), the most malignant of 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 stemnessmarkers. 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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