Bioinformatics analysis identified hub genes in prostate cancer tumorigenesis and metastasis

Abstract

Objective: Prostate cancer (PCa) is the most frequent cancer found in males worldwide, and its mortality rate is increasing every year. To discover key molecular changes in PCa development and metastasis, we analyzed microarray data of localized PCa, metastatic PCa and normal prostate tissue samples from clinical specimens. Methods: Gene expression profiling datasets of PCa were analyzed online. The DAVID was used to perform GO functional and KEGG pathway enrichment analyses. CytoHubba in Cytoscape software was applied to identify hub genes. Survival data were downloaded from GEPIA. Gene expression data were obtained from ONCOMINE and UALCAN. Results: We obtained 4 sets of differentially expressed genes (DEGs), DEGs 1: a comparison of the gene expression between 4 normal prostate and 5 localized PCa samples in GSE27616; DEGs 2: a comparison of the gene expression between 6 normal prostate and 7 localized PCa samples in GSE3325; DEGs 3: a comparison of the gene expression between 5 localized PCa and 4 metastatic PCa samples in GSE27616; DEGs 4: a comparison of the gene expression between 7 localized PCa and 6 metastatic PCa samples in GSE3325. A comparison of these 4 sets of genes revealed 51 overlapped genes. GO function analysis revealed enrichment of the 51 DEGs in functions related to the proteinaceous extracellular matrix and centrosome, protein homodimerization activity and chromatin binding were the main functions of these genes, which participated in regulating cell division, mitotic nuclear division, proteinaceous extracellular matrix, cell adhesion and apoptotic process. KEGG pathway analysis indicated that these identified DEGs were mainly enriched in progesterone-mediated oocyte maturation, oocyte meiosis and cell cycle. We defined the 16 genes with the highest degree of connectivity as the hub genes in the 51 overlapped DEGs. Cox regression revealed TOP2A, CCNB2, BUB1, CDK1 and EZH2 were related to Disease-free survival (DFS). The expression levels of the 5 genes were 2.232-, 1.786-, 2.303-, 1.699-, and 1.986-fold higher in PCa than the levels in normal tissues, respectively (P ＜ 0.05). We obtained 20 hub genes from DEGs by the comparison of normal prostate tissue vs. localized cancer tissue. Among them, KIF20A, CDKN3, PBK and CDCA2, were expressed higher in PCa than in normal tissues, and were associated with the DFS of PCa patients. Meanwhile, we obtained 20 hub genes from DEGs by the comparison of localized cancer tissue vs. metastatic cancer tissue. Cox regression revealed PLK1, CCNA2 and CDC20, were associated with both the DFS and overall survival of PCa patients. Conclusions: The results suggested that the functions of KIF20A, CDKN3, PBK and CDCA2 may contribute to PCa development and the functions of PLK1, CCNA2 and CDC20 may contribute to PCa metastasis. Meanwhile, the functions of TOP2A, CCNB2, BUB1, CDK1 and EZH2 may contribute to both PCa development and metastasis.