Abstract B062: Transcriptomic analysis of whole blood samples from prostate cancer patients: A comparative study of patients from geographically diverse populations

Abstract

Abstract Introduction: Prostate cancer is the most frequently diagnosed cancer across 112 countries. Among American men, an estimated 299, 010 new cases and 35,250 deaths are projected for 2024. In this study, the transcriptomic profile of prostate cancer patients from geographically and ethnically diverse cohorts (USA-Caucasian, RSA-Black) were compared to identify gene expression patterns associated with prostate cancer. Methods: Whole blood samples were collected from PCa and controls. Controls had the same age-range as PCa with no clinical indication of prostatic disease and serum PSA levels below 1.5 ng/ml. RNA was isolated, sequencing was carried out on Novaseq 6000, and data analyzed using PartekFlow to identify differential gene expression patterns (RSA-PCa: 6, RSA-Control: 6, USA-PCa: 7, USA-Control: 11). qRT-PCR was undertaken on a cohort of 27 biomarkers (PROSTest) related to PCa in whole blood. Results: Differential expression analysis identified distinct patterns in USA and RSA groups. In the USA PCa cohort, 2,193 genes were differentially expressed compared to the controls with fold change (FC) >1, p-value (p) <0.05, while in the RSA PCa cohort, 1,627 genes were differentially expressed compared to the controls. Pathway analyses identified enrichment for immune responsive genes in the RSA cohorts. We identified that 26 of 27 Wren’s PROSTest genes detectable in both groups. RNAseq and normalized PCR gene expression were well- correlated (r=0.44, p=0.0012, n=30 pairs). Conclusion: Based on this RNAseq study, there may be geographic differences related to ethnicity in overall blood RNA gene expression. We specifically identified alterations in immune function gene expression between the USA and RSA. Importantly, PROSTest genes were detected in both populations and exhibited a significant correlation. Development of gene signatures for biomarker discovery should, however, consider specific ethnicities and geographical regions. Citation Format: Srinivas V Koduru, Mark Kidd, Ané Pieters, S E Nagel, Robert P Millar, Abdel B Halim. Transcriptomic analysis of whole blood samples from prostate cancer patients: A comparative study of patients from geographically diverse populations [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B062.