Overexpression of EZH2 is associated with clinicopathological parameters and poor prognosis in gliomas

Abstract

Histone methyltransferase EZH2, primarily localized in the nucleus, mediates constitutive Polycomb repressive complex activity by trimethylating lysine 27 of histone H3 (H3K27me3), leading to gene silencing through canonical and noncanonical mechanisms, resulting in transcriptional repression or activation. Its involvement is crucial in cell growth, proliferation, differentiation, and apoptosis, with its effects linked to the regulation of various targets and signaling pathways. Overexpression of EZH2 alters gene expression and function, thereby facilitating cancer progression. Recent research has identified the potential prognostic role of EZH2 expression in glioma patients. This study assesses the clinicopathological significance and prognostic value of EZH2 expression in gliomas using available data. The mRNA levels of EZH2 in tumor tissues and normal tissues were assessed using timer2.0 and data from CGCA and TGCA. The prognostic significance of EZH2 mRNA expression was determined using Kaplan-Meier plotter. A total of 147 clinical samples from glioma patients underwent immunohistochemistry analysis to evaluate EZH2 protein expression. Cox proportional hazards regression model and Kaplan-Meier survival curves were employed to assess the relationship between EZH2 expression, clinicopathological parameters, and overall survival (OS). Across multiple tumor cohorts, EZH2 was found to be upregulated and amplified in tumor tissues. In high-grade glioma patients, EZH2 expression was significantly increased, and higher EZH2 expression correlated with poorer OS, disease-specific survival (DSS), and progression-free interval (PFI). Therefore, the level of EZH2 may serve as a prognostic biomarker for glioma patients.