Abstract 349P
Background
Nomograms or comparable techniques can be used to determine which patients with primary prostate cancer (PCa) will benefit from extended pelvic lymph node dissection (ePLND). ∼ 80% of patients undergo unnecessary ePLND. This study aimed to identify both whole transcriptomic mRNA and microRNA (miR) signatures in primary PCa tumors that are predictive of presence of regional draining lymph node metastasis (LNM).
Methods
Primary PCa obtained from 88 patients [pN0 (n = 44) and pN1 (n = 44)] were profiled on the same tissue section using 2 different probe-based captured direct Next-Generation Sequencing assays and 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 4-mRNA signature (CHRNA2, NPR3, VGLL3, PAH) was commonly found in primary PCa from patients who had LNM, and then validated using the TCGA-PRAD and GSE220095 datasets. The levels of CHRNA2, NPR3, VGLL3, or PAH were associated with significantly worse outcomes. The 4-mRNA signature significantly identified patients with pN1 status [mRNA 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 PSA values, to the 4-gene signature increased the performance to identify pN1 [our mRNA dataset, AUC = 0.85, p = 2.18e-09; TCGA-PRAD, AUC = 0.72, p = 8.7e-08; and the GSE220095 dataset; AUC = 0.88, p = 4.1e-07]. Paired tissue miR analyses showed that 8-miRs were significantly upregulated in primary PCa of pN1 patients (p < 0.01). The 8-miR signature identified pN1 patients [miR dataset; AUC = 0.86, p = 9.9e-10)], and performance increased with PSA [miR dataset (AUC = 0.86, p = 4.7e-10)]. The combination of 4-mRNA and 8-miRs signatures improved LNM prediction.
Conclusions
The study found 4-mRNA and 8-miRs signatures in PCa primaries of pN1 patients. An informative mRNA/miR-signature profile may complement nomograms for better detection of early stage PCa patients with LNM, and triage patients into better treatment decision-making.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
D.S.B. Hoon.
Funding
Martin and Pauline Collins Family, Ensign Cancer Research Foundation Los Angeles, CA, USA.
Disclosure
All authors have declared no conflicts of interest.