[Genes and signaling pathways related to the biochemical recurrence of prostate cancer: An analysis based on the GEO database].

ABSTRACT

OBJECTIVE: To search for the potential genes associated with the recurrence of prostate cancer (PCa) after radical prostatectomy so as to improve the prognosis of the patient. METHODS: The GSE25136 microarray dataset was downloaded from the Gene Expression Omnibus (GEO), involving 39 recurrent and 40 non-recurrent PCa samples. Differentially expressed genes were identified with the Limma package and screened by hierarchical cluster analysis using the Pheatmap package. The potential functions of the differentiated genes were predicted by gene ontology functional enrichment analysis with the ClueGO module of the Cytoscape software. A protein-protein interaction (PPI) network of the genes was constructed in the Cytoscape using the String website, and the module was analyzed using CytoHubba to understand the interactions between these differential genes and identify the key genes in the protein network. The expressions of the identified genes were verified in PCa and normal prostatic tissues by immunohistochemical staining. RESULTS: Totally 167 differentially expressed genes were up-regulated and 91 down-regulated (P ≤ 0.05) in the recurrent PCa samples, with statistically significant differences from the non-recurrent ones. In the top 50 genes that were most significantly up- or down-regulated and mainly involved in the development of the limbic system and the interferon-gamma-mediated signaling pathway, CASP3 and STAT1 were found to be the key genes in the protein network and confirmed to be differentially expressed in the PCa and normal prostatic tissues by immunohistochemistry. CONCLUSIONS: Strong genetic characteristics were found in the progression of recurrent to non-recurrent PCa. The development of the limbic system and the interferon-gamma-mediated signaling pathway are closely related to the development of recurrent PCa. In addition, CASP3 and STAT1, as the key genes, may play an important role in the diagnosis and treatment of recurrent PCa.