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

Abstract

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.

Integrated Bioinformatics Analysis Identified ASNS and DDIT3 as the Therapeutic Target in Castrate-Resistant Prostate Cancer

“…Previous studies identified that CRPC shows a high incidence of somatic mutations, including PTEN-loss, p53/Rb loss, and Myc amplification/overexpression, which confers enhanced PI3K/Akt signaling and mTOR activation. It has been reported that the PI3K/Akt/mTOR pathway plays a pivotal role in the progression to CRPC from PCa and the maintenance of CRPC [ 17 , 39 ]. Mukherjee et al reported that upregulation of the MAPK pathway is involved in the development of CRPC, as earlier studies have indicated a negative correlation between MAPK gene expression and time to biochemical relapse [ 40 ].…”

“…A better understanding of these mechanisms provides a good opportunity for discovering therapeutic targets in drug development [ 14 , 15 ]. The identification of potential genes related to CRPC development has been demonstrated [ 16 , 17 ]; however, whether they are sufficiently understood remains to be determined.…”

Deciphering the Prognostic and Therapeutic Significance of Cell Cycle Regulator CENPF: A Potential Biomarker of Prognosis and Immune Microenvironment for Patients with Liposarcoma

“…Additionally, CENPI, a constitutive protein of kinetochore, was synergistically upregulated with CENPF (as GSEA results shown), which specifies localization of CENPF to kinetochores and is essential for chromosome segregation and mitosis [ 31 ]. Like CENPF, CENPI is overexpressed in multiple cancers and deciphers worse prognosis [ 67 , 68 , 69 , 70 , 71 ]. Our findings suggest the possibility of a cooperative regulatory relationship between CENPF and CENPE or CENPI, thus they functionally synergistically promote liposarcomagenesis and progression.…”