Abstract PR011: Spatial Mapping of Accessible Chromatin Landscapes in Prostate Cancer

Abstract 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 the contribution of global chromatin remodeling 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 (spatial scATAC-seq) using samples from men who underwent prostatectomy at the Center for Prostate Disease Research/Walter-Reed National Military Medical Center. Our current analysis reveals a similar distribution of genome wide accessible locations between AA and CA men. Leveraging a machine learning-based computational cell typing method called Cellcano to annotate scATACseq data, we identify one immune cluster and three stroma and epithelial subclusters. Focusing on the three epithelial subclusters, we observe clear heterogeneity in each patient independent of race. However, motif analysis indicates a race dependent set of transcription factors. Most significant was a dramatic loss of the CCCTC-binding factor (CTCF) motif in AA men. CTCF is a critical zinc finger protein crucial for regulating gene expression, and organizing 3-dimensional structure of chromatin. This finding was validated by CTCF immunohistochemistry staining in an independent TMA that includes 99 patients including both CA and AA prostatectomy samples. 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-basedvariations in PCa outcomes and may inform the development of personalized treatment strategies to address this critical healthcare challenge. Citation Format: Beatriz German, Kun-Lin Ho, Tri Truong, Jennifer Garbarino, Amina Ali, William Azadze, Sally Elsamanoudi, Colin Ng, Greg Chesnut, Leigh Ellis. Spatial Mapping of Accessible Chromatin Landscapes in Prostate Cancer abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86 (2Suppl): Abstract nr PR011.