| Objectives To explore the key genes and pathways of prostate cancer bone metastasis by bioinformatics,and to provide a new research direction for the prevention and treatment of prostate cancer bone metastasis.Methods 1 The dataset GSE74685 containing 20 cases of prostate cancer bone metastasis and 69 cases of prostate cancer lymph node metastasis was retrieved and screened from the Gene Expression Database(GEO).The Limma package of R software is used to preprocess the original data and screen differentially expressed genes(DEGs).DEGs were analyzed by GO function enrichment and KEGG pathway enrichment analysis through the gene function annotation online tool DAVID.The protein-protein interaction(PPI)network of DEGs was constructed by using the STRING online retrieval tool and Cytoscape software.And the important modules and key genes were screened by using MCODE and cyto Hubba plug-ins.The expression,prognosis and diagnostic value of key genes were verified by HCMDB and GEPIA database.2 Combined with the relationship between resveratrol(Res)and key genes and pathways,we treated prostate cancer DU145 cells with Res,and investigated the effect of resveratrol on prostate cancer bone metastasis by CCK-8 proliferation assay,scratch assay and Transwell invasion assay.Results 1 A total of 131 DEGs 2022 DEGs were selected from the dataset GSE74685,including 842 up-regulated genes and 1180 down-regulated genes.GO functional enrichment analysis showed that DEGs were mainly enriched in the extracellular matrix organization,collagen catabolic process,response to mechanical stimulus,and positive regulation of neutrophil chemotaxis.KEGG pathway enrichment suggested that focal adhesion,ECM-receptor interaction,systemic lupus erythematosus and proteoglycan in cancer was the main signal pathway for DEGs enrichment.Eleven key genes,EZH2,PLG,SRC,CAV1,CHD4,HIST2H2 BE,KDM1A,POLR2 E,VWF,APOE,and THBS1,were obtained through PPI network screening.The gene expression of 11 key genes was confirmed to be different between bone and lymph node metastases of prostate cancer(P<0.05).Among them,APOE,EZH2 and SRC were associated with progression-free survival or overall survival,and the AUC values of the three genes were all greater than0.50,showing good diagnostic performance for bone metastasis of prostate cancer.2CCK-8 results showed that Res could inhibit the proliferation of DU145 cells in a concentration-dependent manner.Transwell invasion assay showed that the number of cells crossing the chamber in Res group was less than that in ethanol group(P<0.05),indicating that Res had an inhibitory effect on the invasion ability of DU145 cells.The scratch test showed that the scratch area of the Res group was larger than that of the ethanol group after 24 h,and the repair ratio was significantly smaller than that of the ethanol group(P<0.001),indicating that Res could effectively inhibit the migration ability of DU145 cells.Conclusions 1 There were 2022 differentially expressed genes in bone metastasis and lymph node metastasis of prostate cancer,and these genes mainly acted through adhesion plaque and ECM-receptor interaction signaling pathways.Among them,the key genes EZH2,APOE and SRC are associated with prognosis and have good diagnostic performance,which may be potential targets for prognostic evaluation,diagnosis and treatment of prostate cancer bone metastasis.2 Resveratrol may be a potential therapeutic agent for prostate cancer bone metastases.Figure [11];Table [1];Reference [155]... |
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