Title |
ZEB1 expression is increased in IDH1-mutant lower-grade gliomas
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Published in |
Journal of Neuro-Oncology, August 2016
|
DOI | 10.1007/s11060-016-2240-8 |
Pubmed ID | |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 25% |
Portugal | 1 | 25% |
Unknown | 2 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 24 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 6 | 25% |
Researcher | 4 | 17% |
Student > Bachelor | 3 | 13% |
Student > Master | 2 | 8% |
Lecturer | 1 | 4% |
Other | 3 | 13% |
Unknown | 5 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 8 | 33% |
Biochemistry, Genetics and Molecular Biology | 7 | 29% |
Neuroscience | 2 | 8% |
Agricultural and Biological Sciences | 2 | 8% |
Unknown | 5 | 21% |