Abstract 693: Comparative gene signature between NEPC and CRPC transcriptomics

Abstract Introduction: Prostate cancer (PCa) is the most common cancer in men, with an estimated 299, 010 new cases and 32, 250 deaths projected in 2024. Approximately 1 in 8 men will be diagnosed with PCa, with the majority (60%) occurring in those aged 65 or older. Castration-resistant prostate cancer (CRPC) represents an advanced stage of PCa, with up to 30% of these cases classified as neuroendocrine prostate cancer (NEPC). Previous studies have demonstrated that DNA methylation, chromatin integrity, and transcriptional regulation play crucial roles in the development of treatment-resistant PCa. In this study, we aim to apply next-generation sequencing (NGS) to identify gene signatures regulated in CRPC and NEPC using whole blood samples from patients to discover circulating RNAs and their dysregulated pathways. Methods: Whole blood samples were collected from NEPC (n=9), CRPC (n=5), and healthy controls (n=11). Total RNA was extracted using TRIzol and RNeasy kits, with quality control assessed via Bioanalyzer. RNA-seq was performed on a NovaSeq 6000 platform, and data were analyzed using PartekFlow with High Performance computing system (HPC) to identify differential gene expression patterns. Pathway analysis was conducted on the differentially expressed genes. Results: RNA-seq analysis revealed significant differences in gene expression between NEPC, CRPC, and healthy controls. In total, 4, 655 genes were found to be significantly differentially expressed (fold change >1; P<0.05) in NEPC, and 2, 944 genes in CRPC. Notably, 28% of the statistically significant genes overlapped between NEPC and CRPC. Additionally, analysis of the Wren's PROSTest (27 genes) and NETest (55 genes) signatures identified 25 and 43 genes in NEPC, and 23 and 41 genes in CRPC, respectively, within the differentially expressed gene sets. Conclusion: Our transcriptomic data reveal that NEPC and CRPC share approximately 28% of their gene signatures, with significant correlation to the PROSTest and NETest gene panels. This highlights the potential of these gene signatures as diagnostic tools in identifying and understanding the progression of advanced prostate cancer. Citation Format: Srinivas V. Koduru, Mark Kidd, Abdel Halim. Comparative gene signature between NEPC and CRPC transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 693.