Bioinformatics Analysis Of Bone Metastasis Related Genes In Prostate Cancer

Objectives Prostate cancer is the most common cancer in men,with the fifth highest number of deaths in the world and the tenth in China.More than 80% of advanced prostate cancer-related deaths are caused by frequent bone metastases.Therefore,it is an urgent task to reveal the specific molecular mechanism of bone metastasis of prostate cancer.The combination of microarray technology and bioinformatics analysis has become an effective means to explore the molecular mechanism of various cancers,in order to more accurately and comprehensively reveal the mechanism of bone metastasis of prostate cancer at the molecular level.explore new clinical markers and potential therapeutic targets.Methods In this study,through Shambhala’s cross-platform standardization,the three microarray datasets GSE32269,GSE74685,and GSE60329 for bone metastasis of prostate cancer and primary localized prostate cancer downloaded from GEO,According to the difference multiple of more than 2 times and P value <0.05 to screen the difference gene(DEG)of each data set,and then use the online free analysis tool DAVID to perform GO enrichment and KEGG pathway analysis on these differential genes,and analyze these differential genes The potential biological function of Finally,a protein-protein interaction(PPI)network of differential genes expressed in bone metastasis of prostate cancer was constructed through the STRING online tool,and then all differential genes were submitted to Cytoscape software for network visualization and central gene(HUB gene)identification,Sort the nodes in the network through 12 topological analysis methods(including MCC,DMNC,MNC and EPC)in the cyto Hubba plug-in,and then screen out the genes that interact most closely with other proteins according to Degree,Closeness centrality,and Betweenness centrality.Results In this study,a total of 1092 differential genes were screened from three microarray data sets GSE32269,GSE74685 and GSE60329,downloaded from GEO through cross-platform standardization by Shambhala method,of which 497 genes were up-regulated and 595 genes were down-regulated.Then we further adjusted the threshold to improve accuracy and importance,and screened out 502 genes with more differences for follow-up analysis,of which 195 genes were up-regulated and 307 genes down-regulated.In order to clarify the potential biological function of these differential genes,we clarify the function and metabolic pathway of these differential genes from three aspects:biological process(BP),molecular functional(MF)and cellular component(CC).From the GO enrichment results,it was found that most of these differential genes were located in exocrine body,cytoplasmic matrix,extracellular space,cell membrane,performing protein binding function,and involved in many biological processes such as RNA polymerase II promoter transcription,cell adhesion,muscle contraction,extracellular matrix tissue,senescence,translation initiation and so on.At the same time,our KEGG pathway enrichment analysis results suggest that these gene enrichment pathways are mainly involved in PI3K-Akt signal pathway,cancer pathway,adhesion plaque,Fox O signal pathway,c AMP signal pathway and other signal pathways.Finally,the PPI network of the 502 differentially expressed genes in bone metastasis of prostate cancer was analyzed by STRING online tool,and then the 22 Top genes most closely interacting with other proteins were selected according to the first 5% of Degree,Closeness centrality and Betweenness centrality.According to the above criteria,12 overlapping genes were identified as the central gene(HUB gene)in the PPI network.Among them,nine HUB genes such as IGF1 R,CD44,FOS,EGR1,LDLR,PTGS2,ACTA1,CFTR and ACTA2 were down-regulated,while three genes FN1,MMP9 and CLTC were up-regulated.These genes and related expressed proteins may be the key sites in the process of bone metastasis of prostate cancer.Conclusions 1.The occurrence of prostate cancer bone metastasis is relatively complicated,and its mechanism is not fully understood.It presents the characteristics of multi-step,multi-stage,multi-pathway,and multi-gene complex.This study found the genes related to prostate cancer bone metastasis from the GO enrichment results Most of them are located in exosomes,cytoplasmic matrix,extracellular space,cell membrane,perform protein binding functions,and participate in RNA polymerase II promoter transcription,cell adhesion,muscle contraction,extracellular matrix organization,senescence,and translation initiation And other biological processes.KEGG pathway enrichment analysis results suggest that these gene enrichment pathways mainly involve PI3K-Akt signaling pathway,pathways in cancer,focal adhesion,Fox O signaling pathway,c AMP signaling pathway and other signaling pathways.Prostate bone cancer metastasis may be related to these biological processes.It is closely related to the pathway.2.Through bioinformatics mining and screening of 12 prostate cancer bone metastasis-related HUB genes,IGF1 R,CD44,FOS,EGR1,LDLR,PTGS2,ACTA1,CFTR,ACTA2 and other 9 HUB gene expression down-regulated,FN1 The expression of3 genes,MMP9,CLTC,are up-regulated.These genes and related expression proteins may be the key sites that play a role in the process of prostate cancer bone metastasis,which provides the next step to understand the specific mechanism of these genes in prostate cancer bone metastasis.It also provides new ideas for the mechanism and therapeutic targets of other tumor bone metastases.Figure7;Table7;Reference 128...