Identification of biomarkers, pathways and potential therapeutic target for docetaxel resistant prostate cancer

Abstract

ABSTRACT Docetaxel has been proved to provide survival benefit for advanced prostate cancer (PCa) patients. Resistance to docetaxel further reduces the survival of these patients. Herein, we performed a comprehensive bioinformatic analysis to identify differentially expressed genes (DEGs) between docetaxel sensitive and resistant PCa (DRPC) cell based on Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied for functional and pathway analysis of DEGs. The STRING database, cytoscape software and plug-in ‘cytoHubba’ were used to construct protein–protein interaction (PPI) networks and identify hub genes. Survival analysis were performed via GEPIA database. Finally, we conducted immune infiltration analysis by TIMER. A total of 460 DEGs were identified. GO functional analysis showed that these DEGs are mainly enriched in chemotaxis, negative regulation of intracellular signal transduction, and regulation of cell adhesion, positive regulation of inflammatory response, regulation of response to cytokine stimulus. According to the results of KEGG pathway analysis, these DEGs are mainly involved in signaling by Rho GTPases, Miro GTPases and RHOBTB3; interferon Signaling; arginine biosynthesis; PI3K-Akt signaling pathway; cytokine-cytokine receptor interaction; MAPK signaling pathway. Finally, CCNB1 and EZH2 were identified as prognostic hub genes and the expression of these two genes were associated with immune infiltration. The present study may helps to improve the understanding of the molecular mechanisms of DRPC and facilitate the selection of therapeutic and prognostic biomarkers for DRPC.