Abstract

Enhancer of zeste homologue 2 (EZH2) is a potential independent mechanism for epigenetic silencing of tumor suppressor genes in cancer. We conducted an electronic search on PubMed, EMBASE, Web of Science, and Cochrane library to perform this up-to-date meta-analysis. Fifty-one studies with a total of 9444 patients were included. The prevalence of high EZH2 expression was 0.54 (95% CI: 0.47-0.61). High EZH2 expression was significantly associated with poorer prognosis [overall survival: HR 1.54 (95% CI: 1.30-1.78), P < 0.000; disease free survival: HR 1.35 (95% CI: 1.00-1.71), P < 0.000]. In breast cancer, high EZH2 expression correlated with histological types [OR: 1.53 (95CI: 1.13-2.06); P < 0.006], histological grade [OR: 1.62 (95CI: 1.35-1.95); P < 0.000], estrogen receptor (ER) negativity [OR: 2.05 (95CI: 1.67-2.52); P < 0.000], progesterone receptor (PgR) negativity [OR: 1.42 (95CI: 1.03-1.96); P = 0.034], HER-2 positivity [OR: 1.35 (95CI: 1.08-1.69); P = 0.009], and high p53 expression [OR: 1.66 (95CI: 1.07-2.59); P = 0.024]. These results suggest that high EZH2 expression may be a promising prognostic factor to different cancers. High EZH2 expression tends to correlate with pathological types, histological grade, ER negativity, PgR negativity, HER-2 positivity and p53 high expression in breast cancer.

Highlights

  • Enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 of histone 3 (H3K27)[1]

  • Sixteen of 51 studies were in breast cancer, 10 studies were in lung cancer, 7 studies were in colorectal cancer (CRC) and other 21 studies were about digestive, gynecological and urinary cancers

  • The results indicated that EZH2 highly expressed in 18 kinds of human cancers and the incidence of high EZH2 expression was 0.54

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Summary

Introduction

Enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 of histone 3 (H3K27)[1]. Previous studies have showed that high expression of EZH2 was correlated with aggressiveness, metastasis, and poor prognosis in breast, prostate, bladder and renal cell cancer[11,12,13]. There have been already a metaanalysis on this issue, several important articles are not included in that paper and the subgroup analysis give little useful information[22] We performed this up-todate systematic review with meta-analysis on the influence of high EZH2 expression on the outcomes of different cancers, as well as the incidence of high EZH2 expression, www.impactjournals.com/oncotarget and to provide an overview of the current status of high EZH2 expression in tumor progression and therapy

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