Overexpression of ZEB1 and YAP1 is related to poor prognosis in patients with gliomas with different IDH1 status.

Objective: Whether there is a correlation between zinc-finger E-box-binding homolog 1 (ZEB1) and Yes-associated protein 1 (YAP1) with clinical outcome in gliomas remains unclear. Hence, this study aimed to investigate the effects of ZEB1 and YAP1 on the prognosis of human gliomas and its relationship with the isocitrate dehydrogenase 1 (IDH1) gene state.

Methods: Immunohistochemical staining was used to record the expression levels of ZEB1, YAP1, and p-YAP1 in 122 cases of low-grade glioma (LGGs) and 69 cases of glioblastoma (GBMs). The correlations of ZEB1 and YAP1 with pathological data were determined by Pearson's Chi-square test. Spearman correlation analysis was then used for analyzing the relationship among YAP1, ZEB1, and IDH1 gene status. The effects of ZEB1 and YAP1 on prognosis were investigated through survival analysis.

Results: We detected high ZEB1 expression levels in 29 LGGs (23.8%) and 39 GBMs (56.5%), and high YAP1 expression levels in 22 LGGs (18.0%) and 44 of GBM (63.8%). These results revealed that the protein expression levels of ZEB1 and YAP1 were higher in GBM ( < 0.001). There was a significantly positive correlation between ZEB1 and YAP1 ( < 0.001; r = 0.533). High ZEB1 expression was related to tumor grade ( < 0.001) and Ki-67 ( = 0.0037). YAP1 overexpression was correlated with Ki-67 ( < 0.001), P53 ( = 0.009), tumor grade ( < 0.001), and tumor location ( = 0.018). Patients with ZEB1 and YAP1 high expression had worse overall survival (OS) ( < 0.001). The multivariate analysis showed that YAP1 was an independent prognostic factor for OS. In the LGG group, worse OS were observed in glioma patients with elevated YAP1 expression level. Spearman correlation analysis revealed no association between ZEB1 expression and IDH1 state ( = 0.360; r = -0.084), and YAP1 expression had a negative correlation with IDH1 mutation ( < 0.001, r = -0.364).

Conclusions: Our study showed that ZEB1 and YAP1 were significantly activated in GBM, and patients with high ZEB1 and YAP1 expression had worse OS. ZEB1 expression was significantly correlated with YAP1 in glioma. ZEB1 and YAP1 coexpression may serve as a useful prognostic biomarker for glioma, and aberrant YAP1 expression may be associated with IDH1 gene state.