Abstract C086: Prostate cancer: Integrative multi-omics profiling in patients of African descent
Authors: Elhussin Isra , Baraban Ezra , Lotan Tamara L. , Marshall Cathy Handy , Antonarakis Emmanuel , Campbell Moray J. , Davis Melissa , Dixon Michael , Kim Isaac , Ambs Stefan , Kittles Rick , Murphy Adam B. , Yates Clayton 
Published: December 2023

In the United States and globally, prostate cancer (PCa) mortality rates are highest among men of African descent. Previous studies suggested that tumor subtypes or gene expression profiles had the greatest influence on overall racial/ethnic survival accounting for 24% of the disparities in PCa and remains even when controlled for access to care and stage at presentation. Moreover, the tumor microenvironment plays an essential role in tumor progression, aggressiveness, therapeutic response, and patient outcomes. Additionally, the association of the genomic findings with patient ancestry and other characteristics, such as tumor biology and transcriptomic alterations, remains poorly understood. Here we performed a multi-Omics approach to unravel the complexity of tumor heterogeneity and understand disease progression & distinct tumor biology influenced by genetic ancestry. We performed Spatial NanoString high-plex GeoMx-DSP (Digital Spatial Profiler) at the protein and RNA levels for a total of 118 treatment-naive PCa patients (around 500 ROIs). Simultaneously, we ran matched genome-wide sequencing (whole transcriptome) for these patients. The cohort comprised 87 AAM, 3 unknown, and 28 EAM self-reported individuals. To verify the self-reported race, the genomic ancestry was qualified using genotype and Admixture analysis. To further validate differentially expressed genes at the protein level, we performed multi-plex histological staining of 40 markers to determine the spatial resolution and neighborhood clustering within the tumor and the microenvironment. In parallel, we performed scMultiOmics sequencing (scRNA & scATAC-Seq) at a single-cell resolution (6000 cells/sample at 25K reads per cell) from an additional 12 patients (9 AAM & 3 EAM). We will use the multi-omics integration method (CoGap) to build a structural, spatial map that reflects tissue/system phenotype and to understand the complementary role of multi-omics (genome, transcriptome, and metabolite) interrelation/influence on the disease processes. Our results demonstrate that patients who self-report as AAM or Nigerian are assigned to high African (&gt; 70%) Ancestry with either Yoruba (Nigeria) and/or Bantu subpopulation in the Sub-Saharan area. Additionally, high African Ancestry patients are diagnosed at a younger age and show advanced pathology stages compared to patients with European Ancestry.   Moreover, AAM with high African Ancestry has significantly (p-value 0.05) higher CD8 +ve cells infiltration. Interestingly, segmentation and gating of the immune cell populations showed increased expression of CD8+ve cells colocalization with PD-1 signaling within African Ancestry patients. Our study provides new insight into how genetic ancestry impacts immune signatures in AAM and contributes to PCa racial disparities. Our findings could lead to new therapeutic strategies using immune modulators drugs to decrease the global disease burden, especially among men at high risk for PCa, such as AAM of African descent.

Citation Format: Isra Elhussin, Ezra Baraban, Tamara L. Lotan, Cathy Handy Marshall, Emmanuel Antonarakis, Moray J. Campbell, Melissa Davis, Michael Dixon, Isaac Kim, Stefan Ambs, Rick Kittles, Adam B. Murphy, Clayton Yates. Prostate cancer: Integrative multi-omics profiling in patients of African descent [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C086.