Integrative network analysis to identify hub genes in metastatic prostate cancer

Abstract
Metastatic prostate cancer is the leading cause of prostate cancer related deaths in men around the globe. We performed a detailed bioinformatic analysis to identify the genes involved in the metastasis of the prostate cancer. After identifying the prominent genes that may be involved in metastatic mechanism, we identified purposable drugs, targeting those genes. We identified DEGs using GEO databases. The DEGs thus obtained were validated using TCGA datasets available at GEPIA and TACCO databases. About 14 genes were found to be common in all three databases i.e., GEO, GEPIA and TACCO. Furthermore, we performed GO and KEGG enrichment analyses using DAVID database. PPI-network was constructed using STRINGS software. This network was then analyzed using Cytoscape software. Two plug-ins which were already present in CytoHubba were used for this purpose. The plug-in CytoHubba was used for identifying hub genes and the plug-in MCODE was used for the formation of clusters. Among top 10 hub genes, four genes, ADCYS, PRKG1, ESPR1 and RBFOX2, were present in 2 MCODE clusters. These 4 genes were then used as targets to identify suitable drugs from 3 databases, CMap, DrugBank and TTD. The results identified potential drugs against ADCYS and PRKG1 genes. The effectiveness of the drugs against these two genes were then analyzed by performing Molecular Docking using MOE software.
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