Coexpression Analysis of the EZH2 Gene Using The Cancer Genome Atlas and Oncomine Databases Identifies Coexpressed Genes Involved in Biological Networks in Breast Cancer, Glioblastoma, and Prostate Cancer.

BACKGROUND This study aimed to perform coexpression analysis of the EZH2 gene using The Cancer Genome Atlas (TCGA) and the Oncomine databases to identify coexpressed genes involved in biological networks in breast cancer, glioblastoma, and prostate cancer, with functional analysis of the EZH2 gene in the C4-2 human prostate cancer cell line in vitro. MATERIAL AND METHODS Data from TCGA and Oncomine databases were analyzed to determine the expression of EZH2 and the top five coexpressed genes in breast cancer, glioblastoma, and prostate cancer and the clinical significance the coexpressed genes. Gene Ontology (GO) analysis was performed to predict the functions and pathways of EZH2 using pathway annotation. The role of EZH2 in the C4-2 human prostate cancer cell line was studied in vitro. RESULTS Analysis of 16 micro-arrays identified 185 genes that were coexpressed with EZH2. The top five coexpressed genes were MCM4, KIAA0101, MKI67, RRM2, and CDC25a. Increased expression of these genes and EZH2 were associated with reduced survival. Coexpressed genes were involved in biological networks associated with the cell cycle, mitosis, and DNA damage. The effects of EZH2 on prostate cancer cell was validated in vitro as knockdown of EZH2 resulted in a G2/M cell cycle arrest, increased DNA damage, and reduced colony number. CONCLUSIONS Coexpression analysis of EZH2 identified its role in the cell cycle, mitosis, and DNA repair. The molecular mechanisms involved in EZH2 gene expression in the cell response to DNA damage requires further study to determine whether EZH2 is a potential human cancer biomarker.