Clinical and Genomic Features of Androgen Indifferent Prostate Cancer

作者：Jack Masur, Aakrosh Ratan, Krzysztof Wierbiłowicz, Adanma Ayanambakkam, Michelle L. Churchman, Laura Graham, G. Daniel Grass, Sumati Gupta, Sean Q. Kern, Jennifer King, Zin Myint, Robert J. Rounbehler, Bodour Salhia, Eric A. Singer, Yousef Zakharia, Bryce M. Paschal, Paul V. Viscuse · 发表于：International Journal of Molecular Sciences · 年份：2025 · DOI：10.3390/ijms26020679 · 被引用次数：5 · 研究领域：Prostate Cancer Treatment and Research、Prostate Cancer Diagnosis and Treatment、Cancer, Lipids, and Metabolism

Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics. Our AIPC cohort included three subgroups: aggressive variant prostate cancer (AVPC), neuroendocrine PC (NEPC), and double-negative PC (DNPC). Of 1496 total PC patients available for analysis, we identified 323 (22%) as MCRPC. Of those, 39 (12%) met AIPC criteria (17 AVPC, 13 NEPC, 9 DNPC) and 284 (88%) were non-AIPC. Forty-three percent of AIPC patients had de novo metastatic disease vs. 15% for non-AIPC (p = 0.003). Homologous recombination deficiency (HRD) and tumor mutational burden (TMB) did not differ between cohorts, but microsatellite instability scores (MSI) were significantly higher in AIPC (p = 0.019). Using Gene Set Enrichment Analysis (GSEA), we found that genes defining response to androgens and genes involved in oxidative phosphorylation were the most downregulated, whereas genes involved in epithelial–mesenchymal transition (EMT) and immune signaling were significantly upregulated in AIPC vs. non-AIPC. Our study demonstrates the potential for predefined criteria that aim to enrich for AIPC and suggests opportunities for therapeutic investigation.