High enhancer of zeste homolog 2 correlates with poor prognosis of estrogen receptor-positive breast cancers

Abstract

Objective To observe the biological behaviors of breast cancer expressing defferent levels of histone 3 lysine 27 triple—methylation (H3K27me3), enhancer of zeste homolog 2 (EZH2) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX). Methods The expression levels of H3K27me3, EZH2 and UTX in 146 cases of breast cancer were detected and their prognostic significance was explored. Results H3K27me3 levels were higher in human epidermal growth factor receptor-2 (Her-2)-negative samples. EZH2 expression was higher in breast cancers with lymph node metastasis, diameter >20 mm, and have higher tumor grade and stage. Using a Cox regression model, H3K27me3 and EZH2 levels were independent prognostic factors for overall survival for all the breast cancers [Hazard ratio (HR)=2.57, 95% confidence interval (CI): 1.63-4.04, P<0.01] even the estrogen receptor (ER)-positive subgroup (HR=2.78, 95%CI: 1.52-5.09, P<0.01) in our study. The combination of low H3K27me3 (HR=0.18, 95%CI: 0.07-0.49, P<0.01) and high EZH2 (HR=3.34, 95%CI: 1.20-9.27, P<0.05) was significantly associated with worse survival. UTX level was not significantly associated with prognosis and there were no correlations between H3K27me3 and EZH2/UTX expression. Conclusion Low H3K27me3 and high EZH2 can be used as a prognostic factor for shorter overall survival for breast cancer, including the ER+ breast cancer subtype. Key words: Breast cancer; Histone modification; Enhancer of zeste homolog 2; Prognosis