Dataset Information

Identification of Potential Key Genes and Pathways in Enzalutamide-Resistant Prostate Cancer Cell Lines: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database.

ABSTRACT: Enzalutamide (ENZ) has been approved for the treatment of advanced prostate cancer (PCa), but some patients develop ENZ resistance initially or after long-term administration. Although a few key genes have been discovered by previous efforts, the complete mechanisms of ENZ resistance remain unsolved. To further identify more potential key genes and pathways in the development of ENZ resistance, we employed the GSE104935 dataset, including 5 ENZ-resistant (ENZ-R) and 5 ENZ-sensitive (ENZ-S) PCa cell lines, from the Gene Expression Omnibus (GEO) database. Integrated bioinformatics analyses were conducted, such as analysis of differentially expressed genes (DEGs), Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), and survival analysis. From these, we identified 201 DEGs (93 upregulated and 108 downregulated) and 12 hub genes (AR, ACKR3, GPER1, CCR7, NMU, NDRG1, FKBP5, NKX3-1, GAL, LPAR3, F2RL1, and PTGFR) that are potentially associated with ENZ resistance. One upregulated pathway (hedgehog pathway) and seven downregulated pathways (pathways related to androgen response, p53, estrogen response, TNF-?, TGF-?, complement, and pancreas ? cells) were identified as potential key pathways involved in the occurrence of ENZ resistance. Our findings may contribute to further understanding the molecular mechanisms of ENZ resistance and provide some clues for the prevention and treatment of ENZ resistance.

SUBMITTER: Zheng L

PROVIDER: S-EPMC7382728 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of Potential Key Genes and Pathways in Enzalutamide-Resistant Prostate Cancer Cell Lines: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database.

Zheng Long L Dou Xiaojie X Ma Xiaodong X Qu Wei W Tang Xiaoshuang X

BioMed research international 20200716

Enzalutamide (ENZ) has been approved for the treatment of advanced prostate cancer (PCa), but some patients develop ENZ resistance initially or after long-term administration. Although a few key genes have been discovered by previous efforts, the complete mechanisms of ENZ resistance remain unsolved. To further identify more potential key genes and pathways in the development of ENZ resistance, we employed the GSE104935 dataset, including 5 ENZ-resistant (ENZ-R) and 5 ENZ-sensitive (ENZ-S) PCa c ...[more]

PMID: 32724813

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Project description:BackgroundMen with nonmetastatic, castration-resistant prostate cancer and a rapidly rising prostate-specific antigen (PSA) level are at high risk for metastasis. We hypothesized that enzalutamide, which prolongs overall survival among patients with metastatic, castration-resistant prostate cancer, would delay metastasis in men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level.MethodsIn this double-blind, phase 3 trial, we randomly assigned, in a 2:1 ratio, men with nonmetastatic, castration-resistant prostate cancer and a PSA doubling time of 10 months or less who were continuing androgen-deprivation therapy to receive enzalutamide (at a dose of 160 mg) or placebo once daily. The primary end point was metastasis-free survival (defined as the time from randomization to radiographic progression or as the time to death without radiographic progression).ResultsA total of 1401 patients (median PSA doubling time, 3.7 months) underwent randomization. As of June 28, 2017, a total of 219 of 933 patients (23%) in the enzalutamide group had metastasis or had died, as compared with 228 of 468 (49%) in the placebo group. The median metastasis-free survival was 36.6 months in the enzalutamide group versus 14.7 months in the placebo group (hazard ratio for metastasis or death, 0.29; 95% confidence interval, 0.24 to 0.35; P<0.001). The time to the first use of a subsequent antineoplastic therapy was longer with enzalutamide treatment than with placebo (39.6 vs. 17.7 months; hazard ratio, 0.21; P<0.001; such therapy was used in 15% vs. 48% of patients) as was the time to PSA progression (37.2 vs. 3.9 months; hazard ratio, 0.07; P<0.001; progression occurred in 22% vs. 69% of patients). At the first interim analysis of overall survival, 103 patients (11%) receiving enzalutamide and 62 (13%) receiving placebo had died. Adverse events of grade 3 or higher occurred in 31% of the patients receiving enzalutamide, as compared with 23% of those receiving placebo.ConclusionsAmong men with nonmetastatic, castration-resistant prostate cancer with a rapidly rising PSA level, enzalutamide treatment led to a clinically meaningful and significant 71% lower risk of metastasis or death than placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924 .).

Dataset Information

Identification of Potential Key Genes and Pathways in Enzalutamide-Resistant Prostate Cancer Cell Lines: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database.

Publications

Identification of Potential Key Genes and Pathways in Enzalutamide-Resistant Prostate Cancer Cell Lines: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database.

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