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Updated: May 31, 2025
07:25
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
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Clinical and Genomic Features of Androgen Indifferent Prostate Cancer
Jack Masur1, Aakrosh Ratan2, Krzysztof Wierbilowicz3
1Division of Hematology/Oncology, University of Virginia, Charlottesville, VA 22903, USA.
International Journal of Molecular Sciences
|January 25, 2025
Summary
Androgen-indifferent prostate cancer (AIPC) is a lethal subtype. This study identified AIPC features, finding higher metastatic rates and distinct gene expression patterns, suggesting new therapeutic avenues for this aggressive prostate cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Androgen-indifferent prostate cancer (AIPC) is an aggressive and poorly understood subtype.
- Limited data exists on AIPC characteristics, hindering therapeutic development.
Purpose of the Study:
- To identify and characterize tumors with AIPC features using the ORIEN database.
- To explore molecular differences between AIPC and non-AIPC subtypes.
Main Methods:
- Utilized the ORIEN database to identify AIPC cases based on predefined criteria.
- Subgrouped AIPC into aggressive variant PC (AVPC), neuroendocrine PC (NEPC), and double-negative PC (DNPC).
- Analyzed clinical features, homologous recombination deficiency (HRD), tumor mutational burden (TMB), microsatellite instability (MSI), and gene expression using Gene Set Enrichment Analysis (GSEA).
Main Results:
- Identified 39 AIPC cases (12%) among 323 metastatic castration-resistant prostate cancer (MCRPC) patients.
- AIPC patients showed significantly higher rates of de novo metastatic disease (43% vs. 15%) and higher MSI scores.
- GSEA revealed downregulation of androgen response and oxidative phosphorylation genes, and upregulation of epithelial-mesenchymal transition (EMT) and immune signaling genes in AIPC.
Conclusions:
- Predefined criteria can effectively enrich for AIPC cases.
- AIPC exhibits distinct molecular features, including altered gene expression related to EMT and immune signaling.
- Findings suggest potential therapeutic targets for AIPC, including pathways beyond androgen signaling.
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