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

Area of Science:

• Neuro-oncology
• Cancer Biology
• Molecular Genetics

Background:

• Epithelial-mesenchymal transition (EMT) transcription factors (EMT-TFs) are implicated in epithelial tumor progression but their role in central nervous system tumors remains unclear.
• EMT-TFs are known to promote invasion, chemoresistance, and stem-cell phenotypes in epithelial cancers.
• This study investigates the functional impact of EMT-TFs in grades II-III gliomas.

Purpose of the Study:

• To determine the impact of EMT-promoting transcription factors on overall survival in grades II-III gliomas.
• To compare the expression of EMT-TFs across common genetic subtypes of gliomas.
• To validate findings in a cohort of 31 gliomas.

Main Methods:

• Utilized National Cancer Institute (NCI) Repository for Molecular Brain Neoplasia Data (REMBRANDT) and Cancer Genome Atlas (TCGA) Lower-Grade Glioma (LGG) datasets.
• Performed Kaplan-Meier analysis to assess overall survival (OS).
• Validated findings using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry.

Main Results:

• Increased expression of Zinc Finger E box-binding Homeobox 1 (ZEB1) was associated with significantly increased overall survival (OS) in grades II-III gliomas.
• ZEB1 expression was higher in IDH1/2-mutant gliomas, which showed lower levels of ZEB1 targets and higher levels of microRNA 200C (MIR200C) targets.
• Validation confirmed increased ZEB1 mRNA and protein in IDH1-mutant grades II-III gliomas.

Conclusions:

• A novel relationship exists between IDH1/2 mutations and the expression of ZEB1 and its transcriptional targets in gliomas.
• ZEB1 expression is linked to improved survival in grades II-III gliomas.
• Targeting ZEB1-associated pathways may offer a new therapeutic strategy for these tumors.