Identification and Validation of Three Hub Genes Involved in Cell Proliferation and Prognosis of Castration-Resistant Prostate Cancer

BACKGROUND: The acquisition of castration resistance is lethal and inevitable in most prostate cancer patients under hormone therapy. However, effective biomarkers and therapeutic targets for castration-resistant prostate cancer remain to be defined. METHODS: Comprehensive bioinformatics tools were used to screen hub genes in castration-resistant prostate cancer and were verified in androgen-dependent prostate cancer and castration-resistant prostate cancer in TCGA and the SU2C/PCF Dream Team database, respectively. Gene set enrichment analysis and in vitro experiments were performed to determine the potential functions of hub genes involved in castration-resistant prostate cancer progression. RESULTS: Three hub genes were screened out by bioinformatics analysis: MCM4, CENPI, and KNTC1. These hub genes were upregulated in castration-resistant prostate cancer and showed high diagnostic and prognostic value. Moreover, the expression levels of the hub genes were positively correlated with neuroendocrine prostate cancer scores, which represent the degree of castration-resistant prostate cancer aggression. Meanwhile, in vitro experiments confirmed that hub gene expression was increased in castration-resistant prostate cancer cell lines and that inhibition of hub genes hindered cell cycle transition, resulting in suppression of castration-resistant prostate cancer cell proliferation, which confirmed the gene set enrichment analysis results. CONCLUSIONS: MCM4, CENPI, and KNTC1 could serve as candidate diagnostic and prognostic biomarkers of castration-resistant prostate cancer and may provide potential preventive and therapeutic targets.