Differential gene screening and functional analysis in docetaxel-resistant prostate cancer cell lines

Objective Docetaxel-based combination chemotherapy has traditionally been the standard treatment for metastatic castration-resistant prostate cancer(PCa).However,most patients eventually develop resistance to this treatment,which further reduces their survival.This study aimed to determine key molecular genes in docetaxel-resistant PCa cell lines using bioinformatic approaches.Methods The analysis of microarray data GSE33455(including DU-145/DU-145R and PC-3/PC-3R cell lines)obtained from the Gene Expression Omnibus(GEO)database was performed using GEO2R.Differentially expressed genes(DEGs)of DU-145/DU-145R and PC-3/PC-3R cell lines were selected,and the intersection of DEGs between the two groups was obtained.DEGs were annotated with the Gene Ontology(GO)function and enriched with the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway using an online platform(https://cloud.oebiotech.cn/task/detail/array_enrichment/).The online tool Search Tool for the Retrieval of Interacting Genes(https://string-db.org/)was used to obtain the DEG network graph and matrix list,which was imported into Cytoscape 3.6.1 and analyzed using the Molecular Complex Detection plug-in to detect potential functional modules in the network.Results A total of 131 intersection DEGs were identified between non-treated and docetaxel-resistant PCa cell lines.GO functional annotation showed that the main genes involved were present in the plasma membrane and were involved in positive regulation of ubiquitin-protein transferase activity,positive regulation of pseudopodium assembly,centriolar subdistal appendage,and heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules.KEGG pathway enrichment analysis revealed that DEGs were mainly involved in IL-17 signaling pathway,cytokine-cytokine receptor interaction,rheumatoid arthritis,legionellosis,and folate biosynthesis.We identified two distinct hubs of DEGs:(1)CD274,C-X-C motif chemokine ligand(CXCL)1,DExD/H-box helicase 58,CXCL2,CXCL8,colony-stimulating factor 2,C-X-C motif chemokine receptor 4(CXCR4),CXCL5,and CXCL6 and(2)argininosuccinate lyase,argininosuccinate synthase 1,and asparagine synthetase.Except for the CXCR4 gene that was downregulated,the other 11 genes showed upregulated expression.Conclusion Certain differential genes may be potential targets for predicting and treating metastatic docetaxel-resistant PCa.