| Title |
ZEB1 expression is increased in IDH1-mutant lower-grade gliomas
|
|---|---|
| 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
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 25% |
| Portugal | 1 | 25% |
| Unknown | 2 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
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% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 January 2018.
All research outputs
#15,381,871
of 22,884,315 outputs
Outputs from Journal of Neuro-Oncology
#1,953
of 2,977 outputs
Outputs of similar age
#215,943
of 338,387 outputs
Outputs of similar age from Journal of Neuro-Oncology
#18
of 44 outputs
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