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01-10-2016 | Laboratory Investigation

ZEB1 expression is increased in IDH1-mutant lower-grade gliomas

Authors: Cody L. Nesvick, Chao Zhang, Nancy A. Edwards, Blake K. Montgomery, Michaela Lee, Chunzhang Yang, Herui Wang, Dongwang Zhu, John D. Heiss, Marsha J. Merrill, Abhik Ray-Chaudhury, Zhengping Zhuang

Published in: Journal of Neuro-Oncology | Issue 1/2016

Abstract

Transcription factors that induce epithelial-mesenchymal transition (EMT) promote invasion, chemoresistance and a stem-cell phenotype in epithelial tumors, but their roles in central nervous system tumors are not well-understood. We hypothesized these transcription factors have a functional impact in grades II–III gliomas. Using the National Cancer Institute (NCI) Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the Cancer Genome Atlas (TCGA) Lower-Grade Glioma (LGG) data, we determined the impact of EMT-promoting transcription factors (EMT-TFs) on overall survival in grades II–III gliomas, compared their expression across common genetic subtypes and subsequently validated these findings in a set of 31 tumors using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. Increased expression of the gene coding for the transcriptional repressor Zinc Finger E box-binding Homeobox 1 (ZEB1) was associated with a significant increase in overall survival (OS) on Kaplan–Meier analysis. Genetic subtype analysis revealed that ZEB1 expression was relatively increased in IDH1/2-mutant gliomas, and IDH1/2-mutant gliomas expressed significantly lower levels of many ZEB1 transcriptional targets. Similarly, IDH1/2-mutant tumors expressed significantly higher levels of targets of microRNA 200C (MIR200C), a key regulator of ZEB1. In a validation study, ZEB1 mRNA was significantly increased in IDH1-mutant grades II–III gliomas, and ZEB1 protein expression was more pronounced in these tumors. Our findings demonstrate a novel relationship between IDH1/2 mutations and expression of ZEB1 and its transcriptional targets. Therapy targeting ZEB1-associated pathways may represent a novel therapeutic avenue for this class of tumors.

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Title: ZEB1 expression is increased in IDH1-mutant lower-grade gliomas
Authors: Cody L. Nesvick
Chao Zhang
Nancy A. Edwards
Blake K. Montgomery
Michaela Lee
Chunzhang Yang
Herui Wang
Dongwang Zhu
John D. Heiss
Marsha J. Merrill
Abhik Ray-Chaudhury
Zhengping Zhuang
Publication date: 01-10-2016
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-016-2240-8

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ZEB1 expression is increased in IDH1-mutant lower-grade gliomas

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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