Identification And validation of transcription factor genes involved in prostate cancer metastasis

Metastasis is one of the most significant independent risk factors that can negatively affect prostate cancer (PCa) patients. However, the exact mechanisms have not been fully elucidated. To illustrate the mechanisms underlying PCa metastasis, we conducted a series of integrated bioinformatics analyses. The essential genes involved in PCa metastasis were obtained by analyzing differentially expressed genes (DEGs) between metastatic PCa and localized PCa. Gene Ontology and KEGG pathway enrichment analysis were performed for functional annotation. Protein–protein interaction networks were constructed for hub gene selection. Three transcription factor genes (FOS, CENPA, and FOXM1) were identified by integrating the hub genes with human transcription factors from The Human Transcription Factors database. Moreover, expression validation and prognostic analysis of the three transcription factor genes were carried out on GEO, TCGA, GEPIA, and the Human Protein Atlas, respectively. Further verification showed that expression variation of the three transcription factor genes existed between metastatic PCa and localized PCa as well as between localized PCa and normal prostate. In addition, different expressions of the three transcription factor genes were associated with the prognosis of localized PCa. In summary, the three transcription factor genes can serve as potential prognostic biomarkers as well as therapeutic targets for PCa.
Abbreviations: PCa: prostate cancer; DEGs: differentially expressed genes; TFs: transcription factors; GEO: Gene Expression Omnibus; FC: fold change; DAVID: Database for Annotation, Visualization, and Integrated Discovery; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BP: biological process; CC: cell component; MF: molecular function; PPI: protein–protein interaction; MCODE: Molecular Complex Detection; GEPIA: Gene Expression Profiling Interactive Analysis; GTEx: Genotype-Tissue Expression; TCGA: The Cancer Genome Atlas Program; MCC: Maximal Clique Centrality; DMNC: Density of Maximum Neighborhood Component; MNC: Maximum neighborhood component; EPC: Edge Percolated component; DFS: disease-free survival; OS: overall survival; MAPK: mitogen-activated protein kinases