High Oct4 expression: implications in the pathogenesis of neuroblastic tumours.

Autores de INCLIVA

• 

  Ezequiel Monferrer Garzarán

  Autor

• Rebeca Burgos Panadero

  Autor

• Maria Teresa Blanquer Maceiras

  Autor

• 

  Samuel Navarro Fos

  Autor

• 

  Rosa Noguera Salva

  Autor

Participantes ajenos a INCLIVA

• Cañete A

Grupos y Plataformas de I+D+i

• Grupo de Investigación Translacional de Tumores Sólidos Pediátricos

  

  Leading Researcher

  Samuel Navarro Fos

Abstract

BackgroundNeuroblastic tumours (NBTs) are paediatric solid tumours derived from embryonic neural crest cells which harbour their own cancer stem cells (CSC). There is evidence indicating that CSC may be responsible for tumour progression, chemotherapy resistance and recurrence in NBTs. Oct4 is a transcription factor which plays a key role in mammal embryonic development and stem cell fate regulation. The aim of the study is to elucidate the clinical significance of Oct4 in NBTs.MethodsWe studied Oct4 expression in 563 primary NBTs using digital image quantification. Chi-square test was applied to analyse the correlation between histopathology and the Oct4(+) cell percentage. Survival analysis was carried out with Kaplan-Meier curves and log-rank test. Additionally, a multivariate Cox regression analysis with the stepwise backwards (Wald) method was undertaken to calculate the impact of Oct4 expression level on survival.ResultsWe found that tumours with a high proportion of cells expressing Oct4 correlated statistically with undifferentiated and poorly differentiated neuroblastoma / nodular ganglioneuroblastoma, and that Oct4 expression was not present in ganglioneuroma (p<0.05). Statistical analysis also indicated a relationship between high Oct4 expression levels, high-risk patients according to the International Neuroblastoma Risk Group pre-treatment classification parameters, larger blood vessels and low survival rates.ConclusionsThese results suggest that the Oct4 gene may regulate NBT pathogenic differentiation pathways, and should thus be considered as a target for knockdown when developing novel therapies for high-risk NBT patients.

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Keywords

• Oct4; Digital image analysis; Neuroblastic tumours