Abstract 5929: High performance miRNA and mRNA signatures that in combination with serum PSA levels predict prostate cancer patients with lymph-node invasion

Background: Nomograms or comparable techniques can be used to determine patients with primary prostate cancer (PCa) which are more likely to have lymph node metastasis (LNM) and will benefit from extended pelvic lymph node dissection (ePLND). However, ∼80% of PCa patients undergo unnecessary ePLND, and PCa patients suffer from post-surgical morbid complications. This study aimed to identify both whole transcriptomic mRNA and microRNA (miR) signatures in primary PCa tumors that are associated with the development of regional draining LNM. Methods: Primary PCa obtained from 88 patients [pN0 (n = 44) and pN1 (n = 44)] were profiled using the same tissue section by two different probe-based captured direct Next-Generation Sequencing assays targeting 19,398 human mRNA transcripts and 2,083 human miRs, respectively. Bioinformatic analyses and publicly available TCGA-PRAD [pN0 (n = 382) and pN1 (n = 70)] and GSE220095 [pN0 (n = 138) and pN1 (n = 17)] databases were used for verification and validation. Results: A four-mRNA signature (CHRNA2, NPR3, VGLL3, and PAH) was commonly found in primary tumor tissue samples from PCa patients who had LNM. The results were validated using the TCGA-PRAD and GSE220095 datasets. The four-mRNA signature identified PCa patients with pN1 status [HTP dataset (AUC = 0.83, p = 1.54e-08), the TCGA-PRAD (AUC = 0.708, p = 2.4e-07), and the GSE220095 datasets (AUC = 0.83, p = 8.7e-06)]. Adding serum PSA values, to the four-gene signatures increased the performance to identify pN1 [mRNA dataset (AUC=0.8487 p=2.18e-09), the TCGA-PRAD (AUC=0.7150, p=8.66e-08), and the GSE220095 datasets (AUC=0.8772, p=4.09e-07)]. Paired miR analyses showed that eight miRs were significantly upregulated in primary PCa that were pN1 (p < 0.01). The eight-miR signature significantly identified pN1 patients [miR dataset (AUC=0.8568, p=9.86e-10)], and the performance increased with serum PSA [miR dataset (AUC=0.8626, p=4.66e-10)]. When combining the miR/mRNA signatures (miR-663b, CHRNA2, and PAH) with serum PSA levels showed the best performance to distinguish pN1 from pN0 patients. Conclusions: This study found miR/mRNA signatures in primary PCa tumors that in combination with serum PSA levels may complement nomograms for better detection of PCa patients that develop LNM and triage patients into better surgical decision-making. Citation Format: Matias A. Bustos, Kelly K. Chong, Yoko Koh, SooMin Kim, Eleanor Ziarnik, Romela I. Ramos, Gianna Jimenez, David L. Krasne, Warren A. Allen, Timothy G. Wilson, Dave S. B. Hoon. High performance miRNA and mRNA signatures that in combination with serum PSA levels predict prostate cancer patients with lymph-node invasion [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 5929.