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

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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“…In hepatocarcinoma cells, ZEB1 regulated the resistance of Dox and mediated the mesenchymal characteristics 31. In glioma, ZEB1 acted as a transcription factor of Prognosis and Predict 32. Consistent with all the findings, ZEB1 was overexpressed in OC tissues and cell lines, and upregulation of ZEB1 predicted poor prognosis.…”

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“…CHAC1 functioned in the temozolomide response [ 34 ]. Notably, ZEB1 was widely recognized as an accelerating factor for the genesis and invasion of GBM and was inversely correlated with survival [ 35 , 36 ]. In comparison, we found that ZEB1 expression was protective in the risk score.…”

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“…Five-week-old male BALB/c nude mice (Beijing Vital River Laboratory Animal Technology Co., Ltd.) were randomized into two groups (n=5 per group, total=10). Tumor cells (5×10 6 ) were injected into right dorsal flanks of blindly randomized nude mice (n=5, 1×10 6 per mice), respectively. Every 5 days, we measured the tumor's longitudinal diameter and latitudinal diameter using a caliper.…”

“…Transcription factors (TFs) are major contributors to cancer progression and prognosis [4,5]. For instance, Edwards et al revealed that ZEB1 serves as a TF that is prognostic and predictive in diffuse gliomas [6]. Oktay et al indicated that thyroid TF-1 plays a key role in lung adenocarcinoma prognosis [7].…”