Clinical and Genomic Features of Androgen Indifferent Prostate Cancer

Jack Masur; Aakrosh Ratan; Krzysztof Wierbilowicz; Adanma Ayanambakkam; Michelle L. Churchman; Laura S. Graham; George 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

doi:10.3390/ijms26020679

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Clinical and Genomic Features of Androgen Indifferent Prostate Cancer

Journal article

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Peer reviewed

Clinical and Genomic Features of Androgen Indifferent Prostate Cancer

Jack Masur, Aakrosh Ratan, Krzysztof Wierbilowicz, Adanma Ayanambakkam, Michelle L. Churchman, Laura S. Graham, George Daniel Grass, Sumati Gupta, Sean Q. Kern, Jennifer King, …

International journal of molecular sciences, Vol.26(2), 679

01/15/2025

DOI: 10.3390/ijms26020679

PMCID: PMC11765751

PMID: 39859392

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Abstract

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.

Prostate Cancer

Molecular Biology

Genomics

Biomarkers

androgen-indifferent prostate cancer

therapeutic targets

Details

Title: Subtitle: Clinical and Genomic Features of Androgen Indifferent Prostate Cancer
Creators: Jack Masur - University of Virginia
Aakrosh Ratan - University of Virginia
Krzysztof Wierbilowicz - University of Virginia
Adanma Ayanambakkam - University of Oklahoma Health Sciences Center
Michelle L. Churchman
Laura S. Graham - University of Colorado Denver
George Daniel Grass - Moffitt Cancer Center
Sumati Gupta - Huntsman Cancer Institute
Sean Q. Kern - Uniformed Services University of the Health Sciences
Jennifer King - Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Zin Myint - Markey Cancer Center
Robert J. Rounbehler
Bodour Salhia - University of Southern California
Eric A. Singer - The Ohio State University
Yousef Zakharia - University of Iowa
Bryce M. Paschal - University of Virginia
Paul V. Viscuse - University of Virginia
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.26(2), 679
DOI: 10.3390/ijms26020679
PMID: 39859392
PMCID: PMC11765751
NLM abbreviation: Int J Mol Sci
ISSN: 1422-0067
eISSN: 1422-0067
Publisher: MDPI
Language: English
Date published: 01/15/2025
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984775014402771

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