ZEB1 is a transcription factor that is prognostic and predictive in diffuse gliomas

Lincoln A. Edwards, Sungjin Kim, Mecca Madany, Miriam A Nuno, Tom Thomas, Aiguo Li, Dror Berel, Bong Sup Lee, Minzhi Liu, Keith L. Black, Xuemo Fan, Wei Zhang, John S. Yu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: To address the unmet medical need to better prognosticate patients with diffuse gliomas and to predict responses to chemotherapy regimens. Methods: 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. Results: Fifteen percent of diffuse glioma patients had a ZEB1 deletion. ZEB1 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; P < 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. ZEB1 influenced clinical decision making to initiate procarbazine, CCNU, and vincristine treatment. Conclusion: 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.

Original languageEnglish (US)
Article number1199
JournalFrontiers in Neurology
Volume10
Issue numberJAN
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Glioma
Transcription Factors
Lomustine
Procarbazine
Decision Support Techniques
Vincristine
Survival
Neoplasms
Biomarkers
Radiation
Drug Therapy
Clinical Decision-Making

Keywords

  • Copy number
  • Decision curve analysis
  • Diffuse gliomas
  • Glioma stem cells (GSCs)
  • ZEB1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

ZEB1 is a transcription factor that is prognostic and predictive in diffuse gliomas. / Edwards, Lincoln A.; Kim, Sungjin; Madany, Mecca; Nuno, Miriam A; Thomas, Tom; Li, Aiguo; Berel, Dror; Lee, Bong Sup; Liu, Minzhi; Black, Keith L.; Fan, Xuemo; Zhang, Wei; Yu, John S.

In: Frontiers in Neurology, Vol. 10, No. JAN, 1199, 01.01.2019.

Research output: Contribution to journalArticle

Edwards, LA, Kim, S, Madany, M, Nuno, MA, Thomas, T, Li, A, Berel, D, Lee, BS, Liu, M, Black, KL, Fan, X, Zhang, W & Yu, JS 2019, 'ZEB1 is a transcription factor that is prognostic and predictive in diffuse gliomas', Frontiers in Neurology, vol. 10, no. JAN, 1199. https://doi.org/10.3389/fneur.2018.01199
Edwards, Lincoln A. ; Kim, Sungjin ; Madany, Mecca ; Nuno, Miriam A ; Thomas, Tom ; Li, Aiguo ; Berel, Dror ; Lee, Bong Sup ; Liu, Minzhi ; Black, Keith L. ; Fan, Xuemo ; Zhang, Wei ; Yu, John S. / ZEB1 is a transcription factor that is prognostic and predictive in diffuse gliomas. In: Frontiers in Neurology. 2019 ; Vol. 10, No. JAN.
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abstract = "Objective: To address the unmet medical need to better prognosticate patients with diffuse gliomas and to predict responses to chemotherapy regimens. Methods: 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. Results: Fifteen percent of diffuse glioma patients had a ZEB1 deletion. ZEB1 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; P < 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. ZEB1 influenced clinical decision making to initiate procarbazine, CCNU, and vincristine treatment. Conclusion: 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.",
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T1 - ZEB1 is a transcription factor that is prognostic and predictive in diffuse gliomas

AU - Edwards, Lincoln A.

AU - Kim, Sungjin

AU - Madany, Mecca

AU - Nuno, Miriam A

AU - Thomas, Tom

AU - Li, Aiguo

AU - Berel, Dror

AU - Lee, Bong Sup

AU - Liu, Minzhi

AU - Black, Keith L.

AU - Fan, Xuemo

AU - Zhang, Wei

AU - Yu, John S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: To address the unmet medical need to better prognosticate patients with diffuse gliomas and to predict responses to chemotherapy regimens. Methods: 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. Results: Fifteen percent of diffuse glioma patients had a ZEB1 deletion. ZEB1 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; P < 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. ZEB1 influenced clinical decision making to initiate procarbazine, CCNU, and vincristine treatment. Conclusion: 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.

AB - Objective: To address the unmet medical need to better prognosticate patients with diffuse gliomas and to predict responses to chemotherapy regimens. Methods: 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. Results: Fifteen percent of diffuse glioma patients had a ZEB1 deletion. ZEB1 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; P < 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. ZEB1 influenced clinical decision making to initiate procarbazine, CCNU, and vincristine treatment. Conclusion: 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.

KW - Copy number

KW - Decision curve analysis

KW - Diffuse gliomas

KW - Glioma stem cells (GSCs)

KW - ZEB1

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