PATZ1 is a new prognostic marker of glioblastoma associated with the stem-like phenotype and enriched in the proneural subtype

Elia Guadagno, Michela Vitiello, Paola Francesca, Gaetano Calì, Federica Caponnetto, Daniela Cesselli, Simona Camorani, Giorgio Borrelli, Marialuisa Califano, Paolo Cappabianca, Claudio Arra, Elvira Crescenzi, Laura Cerchia, Maria Laura Del Basso de Caro, Monica Fedele

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)59282-59300
Number of pages19
JournalOncotarget
Volume8
Issue number35
DOIs
Publication statusPublished - 2017

Keywords

  • Biomarker
  • Glioma
  • Glioma stem cells
  • PATZ1
  • Tumor heterogeneity

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Guadagno, E., Vitiello, M., Francesca, P., Calì, G., Caponnetto, F., Cesselli, D., Camorani, S., Borrelli, G., Califano, M., Cappabianca, P., Arra, C., Crescenzi, E., Cerchia, L., de Caro, M. L. D. B., & Fedele, M. (2017). PATZ1 is a new prognostic marker of glioblastoma associated with the stem-like phenotype and enriched in the proneural subtype. Oncotarget, 8(35), 59282-59300. https://doi.org/10.18632/oncotarget.19546