Ancestry-Informed Transcriptomic Analysis Identifies YY1 Axis Disruption and Stromal Program Loss in African American Prostate Cancer 2258332
Year: 2026
Type: article
Abstract: Introduction Prostate cancer (PCa) shows racial disparities, with African American (AA) men experiencing higher incidence and worse outcomes than European American men. We investigated ancestry-associated molecular programs to better understand these differences. Methods RNA-seq data from high-grade PCa were analyzed using DESeq2 and GSEA to identify differentially expressed genes and pathways. Candidate genes and pathways were then examined through ongoing wet-lab assays in MDA-PCa-2b and LN-CaP cell-line to evaluate their effect in PCa. Results Multiple genes and pathways exhibited ancestry-associated dysregulation linked to tumor progression and aggressiveness. Notably, several noncoding and pseudogene transcripts, traditionally considered transcriptionally inert, showed reproducible overexpression patterns, suggesting potential epigenetic activation and regulatory cross-talk in AA tumors. Pathway-level findings revealed broad depletion of muscle/contractile programs, robust enrichment of olfactory receptor signaling, and downregulation of YY1 target gene sets, consistent with stroma loss and transcriptional reprogramming observed in experimental models. Conclusion Ancestry-informed transcriptomic analysis identifies chemosensory GPCR activation through olfactory receptor signaling enrichment and loss of stromal support programs, providing a framework for biomarker discovery and therapeutic exploration in AA PCa. These findings highlight transcriptional and microenvironmental alterations that may contribute to tumor aggressiveness and provide a foundation for biomarker discovery and ancestry-tailored therapeutic strategies. Funding Source n/a Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)
Source: The Journal of Immunology
Authors: Roberto Aguilar, Junseok Lee, Grant Adams
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7171487273
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