The role of EZH2 in overall survival of colorectal cancer: a meta-analysis



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Enhancer of zeste homolog 2 (EZH2) is the catalitic subunit of polycomb repressive complex 2 and mediates gene silencing. EZH2 is overexpressed in many cancers and correlates with poor prognosis. The role of the gene EZH2 in colorectal cancer survival is uncertainly, the aim of this study is clear this relationship. Relevant literaure was searched from electronic databases. A meta-analysis was performed with elegible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 8 studies (n = 1059 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with colorectal cancer. Combined hazard ratios suggested that EZH2 overexpression was associated with better prognosis of overall survival (OS) HR(hazard ratio) = 0.61 95% CI (0.38–0.84) We performed bias analysis according Egger and Begg,s test and we did not find publication bias. EZH2 overexpression indicates a better prognosis for colorectal cancer.

Colorectal cancer (CRC) is one of the main causes of death in industrialized countries, coming in third place for incidence and fourth for mortality in the world as a whole1.

Colorectal cancer develops from the progressive accumulation of molecular events, like somatic mutations in oncogenes, or epigenetic mechanisms such as methylation of DNA or post-transcriptional modification of histones2. Over recent years, various studies have focused on the discovery of the molecular changes that participate in the process of tumour development, with the aim of finding biomarkers potentially useful in predicting survival or directing therapeutic strategies3.

One of the mechanisms that regulate histone epigenetic modification is mediated by the polycomb repressive complexes (PcG). PcG are epigenetic modifiers that promote gene repression through modification and compaction of chromatin. Two major complexes, designated as PRC1 and PRC2, perform different functions in cells related to gene silencing4,5. PRC1 includes the sub-units Bmi1, Ring1b, CBX4 and PHC, and induces mono-ubiquitination of the residue of lysine 119 from histone H2. PRC2 is formed by the protein EZH2, a catalytic sub-unit with a methyl-transeferase activity, and the sub-units SUZ12, EED and RbAp48, necessary for maintaining the integrity of the complex6.

It is believed that the EZH2 protein participates in the transcriptional repression of genes through various mechanisms, such as trimethylation of the residue of lysine 27 of histone H3 (H3mek27), or methylation of the CpG islands It also operates as a platform recruiting other enzymes involved in gene silencing, like histone de-acetylases (HDACs)7,8 and methyltransferases (DNMT1, DNMT3A, and DNMT3b)9.

In cancer, EZH2 promotes cell proliferation, invasion, apoptosis, angiogenesis and metastasis, according to the findings of in vitro studies on different cell lines10,11,12,13. Moreover, it has been found over-expressed in the tumour tissues of numerous neoplasias affecting the prostate7,14, breast15, bladder16, ovaries17, small-cell18 and non-small-cell lung cancer19, brain tumours20, kidney cancer21, gastric cancer22, and cancer of the oesophagus23, pancreas24, or melanoma25.

A good number of studies suggest that the over-expression of EZH2 may have a prognostic value in some types of cancer, and it has been associated with a…