ZEB1 Is a Transcription Factor That Is Prognostic and Predictive in Diffuse Gliomas

• Published in: Frontiers in neurology Vol. 9; p. 1199
• Main Authors: Edwards, Lincoln A, Kim, Sungjin, Madany, Mecca, Nuno, Miriam, Thomas, Tom, Li, Aiguo, Berel, Dror, Lee, Bong-Sup, Liu, Minzhi, Black, Keith L, Fan, Xuemo, Zhang, Wei, Yu, John S
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17-01-2019
• Subjects: copy number; decision curve analysis; diffuse gliomas; glioma stem cells (GSCs); Neurology; ZEB1; decision curve analysis; ZEB1; copy number; diffuse gliomas; glioma stem cells (GSCs)
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2018.01199

To address the unmet medical need to better prognosticate patients with diffuse gliomas and to predict responses to chemotherapy regimens.
ZEB1 alterations were retrospectively identified from a cohort of 1,160 diffuse glioma patients. Epigenome-wide association scans (EWAS) were performed on available data. We determined the utility of ZEB1 as a prognostic indicator of patient survival in diffuse gliomas and assessed the value of ZEB1 to predict the efficacy of treating diffuse glioma patients with procarbazine, CCNU, and vincristine along with radiation at diagnosis. Decision curve analysis (DCA) was used to determine if ZEB1 added benefit to clinical decision-making over and above conventional methods.
Fifteen percent of diffuse glioma patients had a
deletion.
deletion was associated with poor overall survival (OS) with and without adjustment for age and tumor grade (adjusted HR: 4.25; 95% CI: 2.35 to 7.66;
< 0.001). Decision curve analysis confirmed that ZEB1 status with or without IDH1 was more beneficial to clinical decision making than conventional information such as age and tumor grade. We showed that ZEB1 regulates TERT expression, and patients with ZEB1 deletions likely subsume patients with mutant TERT expression in diffuse gliomas.
influenced clinical decision making to initiate procarbazine, CCNU, and vincristine treatment.
We demonstrate the prognostic value of ZEB1 in diffuse glioma patients. We further determine ZEB1 to be a vital and influential molecular marker in clinical decisions that exceed conventional methods regarding whether to treat or not treat patients with diffuse glioma.