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Updated: Nov 11, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Molecular mechanisms, immune cell infiltration, and potential drugs for prostate cancer
Yunkun Yan1,2,3,4, Xingning Mao3,5,6, Qingyun Zhang1,2,3
1Institute of Urology and Nephrology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, China.
Background:
The molecular mechanisms involved in the prostate cancer and their relationship with immune cell infiltration are not fully understood. The prostate cancer patients undergoing standard androgen deprivation therapy eventually develop castration resistant prostate cancer (CRPC) for which there is no effective treatment currently available, and the hub genes involved in this process remain unclear.
Objective:
To study prostate cancer systematically and comprehensively.
Methods:
Differentially expressed genes (DEGs) of prostate cancer were screened in The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Connectivity Map (Cmap) software was applied to discover potential treatment drugs. A protein-protein interaction (PPI) analysis was performed to obtained the hub genes, and the relationship between hub genes and immune cell infiltration was investigated. Next, RNAseq data of hormone-sensitive prostate cancer samples and CRPC samples obtained from TCGA database was further analyzed to identify DEGs. Finally, a PPI analysis was performed to obtain the hub genes.
Results:
A total of 319 DEGs were identified between prostate cancer samples and normal adjacent samples from TCGA database using comparative analysis. The KEGG pathway analysis showed significant correlations with drug metabolism, metabolism of xenobiotics by cytochrome P450, and chemical carcinogenesis. AMACR, FOLH1 and NPY, three hub genes, were found to be upregulated. FOLH1 was positively correlated with CD8+ T cell infiltration. FOLH1, AMACR, and NPY were negatively correlated with CD4+ T cell infiltration. A total of 426 DEGs were identified from RNAseq data of hormone-sensitive prostate cancer samples and CRPC samples using further comparative analysis. KEGG pathway enrichment analysis showed significant correlations with arachidonic acid metabolism, PPAR signaling pathway, AMPK signaling pathway, and metabolic pathways. The top 10 hub genes in PPI network were screened out, including PPARG, SREBF1, SCD, HMGCR, FASN, PTGS2, HMGCS2, SREBF2, FDFT1, and INSIG1. Among them, SCD and FASN are expected to be the potential therapeutic targets for CRPC.
Conclusions:
AMACR, FOLH1 and NPY may be effective therapeutic targets and specific diagnostic markers for prostate cancer. AMACR, FOLH1, and NPY are also closely associated with immune cell infiltration in prostate cancer. Moreover, aminoglutethimide and resveratrol were found to be the promising drugs for treating prostate cancer. The progression of hormone-sensitive prostate cancer to CRPC may be related to arachidonic acid metabolism, PPAR signaling pathway, AMPK signaling pathway, and other metabolic pathways. SCD and FASN are expected to be the potential therapeutic targets for CRPC.
Insights
This study identifies key genes (AMACR, FOLH1, NPY) and pathways involved in prostate cancer progression and immune infiltration. It also highlights potential therapeutic targets like SCD and FASN for castration-resistant prostate cancer (CRPC).
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Prostate cancer molecular mechanisms and immune cell infiltration remain poorly understood.
- Castration-resistant prostate cancer (CRPC) develops from standard androgen deprivation therapy, lacking effective treatments.
- Key genes driving CRPC progression are yet to be identified.
Purpose of the Study:
- To comprehensively investigate prostate cancer molecular mechanisms.
- To identify key genes and pathways in prostate cancer development and progression to CRPC.
- To explore potential therapeutic targets and drugs for prostate cancer.
Main Methods:
- Screened differentially expressed genes (DEGs) in prostate cancer using The Cancer Genome Atlas (TCGA) database.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
- Utilized Connectivity Map (Cmap) software for drug discovery and protein-protein interaction (PPI) analysis for hub genes.
- Analyzed RNAseq data from hormone-sensitive and CRPC samples to identify DEGs and hub genes.
Main Results:
- Identified 319 DEGs in prostate cancer; KEGG analysis linked to drug metabolism and chemical carcinogenesis.
- Upregulated hub genes AMACR, FOLH1, and NPY showed correlations with CD8+ and CD4+ T cell infiltration.
- Identified 426 DEGs in CRPC progression; KEGG analysis linked to metabolic pathways (e.g., arachidonic acid, PPAR, AMPK).
- Top 10 hub genes in CRPC include PPARG, SREBF1, SCD, FASN; SCD and FASN are potential therapeutic targets.
Conclusions:
- AMACR, FOLH1, and NPY are potential diagnostic markers and therapeutic targets for prostate cancer, linked to immune infiltration.
- Aminoglutethimide and resveratrol show promise as treatments for prostate cancer.
- Prostate cancer progression to CRPC involves metabolic pathways, with SCD and FASN as potential therapeutic targets.
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