Abstract 2150: Spatial transcriptomic analysis of histologically matched regions adjacent to and within prostate cancer reveals RNA expression differences between African Americans and European Americans
Authors: Vinay Kumar, Dominic Castaneda, James A. Nguyen, Giovanna A. Giannico, Michael M. Ittmann, Patricia Castro, Omid Yazdanpanah, Arash Rezazadeh, Tara S. Jennings, Michael Mcclelland, Farah Rahmatpanah
Journal: Cancer Research (2024)

Abstract Introduction. Prostate cancer (PCa) of American men of African ancestry (AA) is diagnosed at an earlier median age and more advanced stage with a poorer prognosis and significantly higher mortality than in Americans of primarily Northern European ancestry (EA). The mechanism of how ancestry contributes to aggressive PCa in AA patients is not well understood. Given the inherent heterogeneity and multifocality of prostate cancer, Spatial transcriptomics is of particular interest because it allows distinct cell populations within the tumor microenvironment to be characterized, and their possible effects on local tumors to be identified. Here we compare transcription between four AA and four EA patients in regions of peritumoral stroma, inflammation, Benign Prostatic Hyperplasia (BPH), and Gleason score patterns 3 (G3) and 4 (G4). Methods: Formalin fixed, paraffin embedded (FFPE) prostatectomy tissue blocks were obtained from 8 patients (4 AA and 4 EA) prior to treatment of the patients and matched for clinical variables (i.e., biochemical relapse, age, Gleason score, and tumor stage). 10um tissue sections were mounted onto Visium Spatial Gene Expression Slides and processed following 10x Genomics protocol. Sample counts were processed through Space Ranger. 18000 unique genes, spatial barcodes, and clinician guided annotations were imported to the R program Seurat. Data was processed using SCTransform. Significance of each transcript differences between each tissue were calculated. Results: Digital histologic slides of prostate cancer specimens from AA (n=4) and EA (n=4) patients were annotated by a urologic pathologist to identify regions of peritumoral stroma, inflammation, BPH, G3, and G4. Each spot was interrogated for the expression of 18000 transcripts, with an average of 17796 being detected per spot. Among the largest differences observed between AA and EA, G3 and G4 had distinct transcriptome profiles in the four AA as compared to G3 and G4 in four EA. Also, when differential expression (padj &amp;lt; 0.05) in peritumoral stroma was compared to G4 in AA, we identified 290 differentially expressed genes, whereas the same comparison in EA cohorts identified 600 differentially expressed genes. Conclusion: Spatial transcriptomic analysis revealed differences in gene expression across multiple tissue types in prostate cancer patients of different ancestries. Citation Format: Vinay Kumar, Dominic Castaneda, James A. Nguyen, Giovanna A. Giannico, Michael M. Ittmann, Patricia Castro, Omid Yazdanpanah, Arash Rezazadeh, Tara S. Jennings, Michael Mcclelland, Farah Rahmatpanah. Spatial transcriptomic analysis of histologically matched regions adjacent to and within prostate cancer reveals RNA expression differences between African Americans and European Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2150.