Abstract C087: Analysis of the chromatin accessibility landscape in patients with localized prostate cancer

Abstract Significant group-based variations in prostate cancer (PCa) outcomes represents a critical healthcare challenge in the USA. African American (AA) men face the highest incidence of PCa and are twice as likely to succumb to their disease compared to their Caucasian American (CA) counterparts. This disparity stems from a complex interplay involving social, environmental, and biological factors. While inequitable access to quality healthcare is a key contributor, even in settings with equal care, AA patients more often present with advanced disease at diagnosis, suggesting unique tumor biology. While some understanding of the epigenomic landscape has been recently identified, the full extent of global chromatin remodeling contribution towards differences in health outcomes across population groups remains poorly understood. To better elucidate how chromatin remodeling and gene regulation influences PCa development across CA and AA population groups, we employed single-cell spatial transposase-accessible chromatin technology followed by sequencing (scATAC-seq) and H3K27ac spatial-CUT&Tag using samples from men who underwent prostatectomy at the Center for Prostate Disease Research/Walter-Reed National Military Medical Center. Our current analysis revealed significantly greater chromatin accessibility in AA men compared to CA men. Leveraging a machine learning-based computational cell typing method called Cellcano to annotate scATACseq data, enabled the identification of unique cell types and distinct gene score signatures enriched in AA samples compared to CA counterparts. Furthermore, AA demonstrated significant lower accessible chromatin associated with CCCTC-binding factor (CTCF) which is a critical zinc finger protein crucial for regulating gene expression, epigenetic marks, and maintaining 3-dimensional genome structure. We have validated this finding by CTCF immunohistochemistry in an independent TMA that includes 99 patients with distribution of CA and AA prostatectomy samples. Moreover, integration of H3K27ac profiling revealed several differentially regulated enhancer regions near specific genes across samples. Collectively, our current findings provide critical insights into the divergent chromatin accessibility profiles between AA and CA men with localized PCa, which likely underlie distinct transcriptional responses that can determine therapeutic resistance and tumor progression. These data shed light on the complex epigenomic mechanisms driving the group-based variations in PCa outcomes and may inform the development of personalized treatment strategies to address this critical healthcare challenge. Citation Format: Beatriz German Falcon, Kun-Lin Ho, Tri Truong, Jennifer Garbarino, Jiaying Chen, Amina Ali, William Azadze, Sally Elsamanoudi, Colin Ng, Gregory Chesnut, Leigh Ellis. Analysis of the chromatin accessibility landscape in patients with localized prostate cancer [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C087.