Expression of EZH2 is associated with poor outcome in colorectal cancer

Abstract

Enhancer of zeste homolog 2 (EZH2), the critical component of polycomb group protein family, has been demonstrated to be overexpressed in various types of human cancer, including hepatocellular carcinoma, breast, bladder and lung cancer. The mechanism of how EZH2 promotes oncogenesis has also been well studied. However, little is known about the role of EZH2 in colorectal cancer (CRC). The main purpose of the present study was to analyze the association between EZH2 expression and the clinicopathological features of CRC. Therefore, the mRNA and protein expression levels were analyzed in tumor tissues and adjacent non-cancerous tissues by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The expression of EZH2 was demonstrated to be significantly increased in tumor tissues compared with adjacent noncancerous tissues, according to the results of western blot analysis and RT-qPCR in the majority of cases. Patients with low EZH2 expression had a longer overall survival rate compared with those with high EZH2 expression. An analysis of the association between clinicopathological features and EZH2 expression indicated that high EZH2 expression was significantly associated with tumor stage, tumor size, histological differentiation and lymph node metastasis. Multivariate analysis demonstrated that high EZH2 expression was an independent predictor of overall survival. In conclusion, to the best of our knowledge, the data presented in the present study is the first to indicate that EZH2 is upregulated in CRC and may serve as a predictor of poor outcome for patients with CRC.

COCOA: coordinate covariation analysis of epigenetic heterogeneity

“…DNA methylation in EZH2-binding regions positively correlated with cancer stage in 5 of 21 tested cancers, but trended negative in 3 cancer types (Additional file 2: Fig. S8), of which colon adenocarcinoma (COAD) had a significant negative correlation (p < 0.05, t approximation, Holm-Bonferroni correction), consistent with a previous report [35]. To further investigate the significance of the EZH2-binding regions, we used a Cox proportional hazards model to test for association between survival and average DNA methylation in these regions and found a significant association in 5 cancer types (Fig.…”

Clinicopathologic significance of protein lysine methyltransferases in cancer

“…Importantly, this study also found that EZH2 was an independent predictor of decreased overall survival in patients with colorectal cancer after multivariate analysis for lymph node and distant metastasis. These findings were supported by another study of 95 patients with colorectal cancer, in which high protein levels of EZH2 were associated with advanced clinical stage, histologic grade and independently predicted poor overall survival in this patient cohort [12]. Furthermore, Ohuchi et al showed that EZH2 protein expression levels gradually increased from normal colonic mucosa to dysplasia and colorectal cancer, suggesting an oncogenic role for EZH2 in the carcinogenesis process from benign mucosa to carcinoma [13].…”

GAPDH Overexpression in the T Cell Lineage Promotes Angioimmunoblastic T Cell Lymphoma through an NF-κB-Dependent Mechanism

“…EZH2 is increasingly expressed during the progression of hematopoietic and solid cancers (Bachmann et al, 2006;Chen et al, 2018;Karakashev et al, 2018;Patnaik et al, 2018;Sudo et al, 2005), and overexpression of mutant EZH2 has been recognized in a wide selection of B and T cell lymphoproliferative disorders (Morin et al, 2010;Raaphorst et al, 2000;Sasaki et al, 2011;Sneeringer et al, 2010;Visser et al, 2001). Therefore, considerable effort has been directed toward development of EZH2 inhibitors, but current specific EZH2 inhibitors can (B) GSEA for the NF-kB related genes in (A).…”