Identification of hub genes predicting the development of prostate cancer from benign prostate hyperplasia and analyzing their clinical value in prostate cancer by bioinformatic analysis

Abstract

Prostate cancer (PCa) and benign prostate hyperplasia (BPH) are commonly encountered diseases in males. Studies showed that genetic factors are responsible for the occurrences of both diseases. However, the genetic association between them is still unclear. Gene Expression Omnibus (GEO) database can help determine the differentially expressed genes (DEGs) between BPH and PCa. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were utilized to find pathways DEGs enriched. The STRING database can provide a protein–protein interaction (PPI) network, and find hub genes in PPI network. R software was used to analyze the clinical value of hub genes in PCa. Finally, the function of these hub genes was tested in different databases, clinical samples, and PCa cells. Fifteen up-regulated and forty-five down-regulated genes were found from GEO database. Seven hub genes were found in PPI network. The expression and clinical value of hub genes were analyzed by The Cancer Genome Atlas (TCGA) data. Except CXCR4, all hub genes expressed differently between tumor and normal samples. Exclude CXCR4, other hub genes have diagnostic value in predicting PCa and their mutations can cause PCa. The expression of CSRP1, MYL9 and SNAI2 changed in different tumor stage. CSRP1 and MYH11 could affect disease-free survival (DFS). Same results reflected in different databases. The expression and function of MYC, MYL9, and SNAI2, were validated in clinical samples and PCa cells. In conclusion, seven hub genes among sixty DEGs may be achievable targets for predicting which BPH patients may later develop PCa and they can influence the progression of PCa.