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Identification of Potential Key Genes and Pathways in Enzalutamide-Resistant Prostate Cancer Cell Lines: A
Long Zheng1, Xiaojie Dou2, Xiaodong Ma1
1Department of Nuclear Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710004, China.
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-α, TGF-β, complement, and pancreas β 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.
Insights
Enzalutamide resistance in prostate cancer involves key genes and pathways. This study identified 12 hub genes and altered signaling pathways, offering insights into treatment resistance mechanisms.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Enzalutamide (ENZ) is a vital treatment for advanced prostate cancer (PCa).
- Mechanisms of ENZ resistance in PCa are not fully understood, hindering effective long-term treatment.
- Identifying novel molecular targets is crucial for overcoming ENZ resistance.
Purpose of the Study:
- To identify key genes and pathways associated with enzalutamide resistance in prostate cancer.
- To elucidate the molecular mechanisms underlying the development of ENZ resistance.
- To provide potential targets for overcoming treatment resistance.
Main Methods:
- Utilized the GSE104935 dataset comprising enzalutamide-resistant (ENZ-R) and sensitive (ENZ-S) PCa cell lines.
- Performed integrated bioinformatics analyses: differential gene expression, GO, KEGG, PPI, GSEA, and survival analysis.
- Identified differentially expressed genes (DEGs) and hub genes, alongside key signaling pathways.
Main Results:
- Identified 201 DEGs (93 upregulated, 108 downregulated) and 12 hub genes (e.g., AR, ACKR3, GPER1).
- Discovered one upregulated pathway (Hedgehog) and seven downregulated pathways (androgen response, p53, estrogen response, etc.).
- These findings highlight significant molecular alterations in ENZ-resistant PCa.
Conclusions:
- The identified hub genes and pathways are critically involved in prostate cancer enzalutamide resistance.
- These molecular insights can guide the development of strategies to prevent or treat ENZ resistance.
- Further research into these targets may improve therapeutic outcomes for advanced PCa patients.
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