Abstracts from the New England Section of the AUA 2021

© The Canadian Journal of Urology TM : International Supplement, October 2021 Concurrent Poster Session I Inhibitory Effects of STAT3 Transcription Factor by Synthetic DecoyODNs on Autophagy in Renal Fibrosis Kwan-Kyu Park, Professor , Young-Ah Kim, Researcher College of Medicine, Catholic University of Daegu, Daegu, Korea, Republic of Introduction: Autophagy in the proximal tubules may promote fibrosis by activating tubular cell death, interstitial inflammation, and the production of pro-fibrotic factors. The signal transducer and activator of transcription 3 (STAT3) is activated as a potential transcription factor, which mediates the stimulation of renal fibrosis. We investigated the role of the STAT3 in autophagy and its effect on the prevention of interstitial renal fibrosis. Materials & Methods: We use synthesized STAT3 decoy oligonucleotides (ODNs), which were injected into the tail veins of unilateral ureteral obstruction (UUO) mice, to explore the regulation of autophagy in UUO- induced renal fibrosis. The expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and collagenwere decreased by STAT3 decoy ODN. The autophagy markers microtubule-associated protein light chain 3 (LC3) and fibronectin, were identified through immunofluorescent staining, indicating that they were reduced in the group injected with ODN. Results: The expressions of LC3, Beclin1, p62 and autophagy-related 5-12 (Atg5-12) and hypoxia inducible factor-1α (HIF-1α) were inhibited in the ODN injection group. We determined the inhibitory effect of autophagy in chronic kidney disease and confirmed that STAT3 decoy ODN effectively inhibited autophagy by inhibiting the expression of STAT3 transcription factors in the UUO group. Conclusions: Our results suggest that STAT3 decoyODNs may be involved in the regulation of autophagy and fibrosis, and that, thus, they are a promising new therapeutic target in chronic kidney disease. P14 A Standardized Serum Bank for Obtaining Microrna Signatures for Assessing Prostate Cancer Risk Scott Perrapato, DOFACOS , Nicholas Farina, PhD, Adrian Berg, MD, Marcia Wills, MD, Jane Lian, PhD University of Vermont, Burlington, VT, USA Introduction: MicroRNA (miRNA) signatures have been shown to predict long-term risk of breast and other cancers. We hypothesize a subset of cancer- free men at elevated risk (“risk”) for developing prostate cancer (First degree relatives) will have a miRNAsignature which distinguish them from average risk (“no risk”) individuals. Materials & Methods: 1) Serum miRNA development serum microRNA collection, processing, storage (tissue bank) and analysis by recent technologies that are reproducible; 2) Identify microRNA profiles in men at elevated risk for prostate cancer that are distinct from controls; 3) Determine the effect of time from collection, ejaculation and symptomatic benign prostatic hyperplasia on a miRNA signature; 4) Compare in-house qPCR analysis with FirePlex™ Technology to validate miRNA signature components; 5) Determine the relationships between clinical elevated risk categories that are associated with signature miRNAs. Results: This pilot study enrolled a total of 68 cancer-free men, 51 with average risk of prostate cancer and 17 having elevated risk with a family history (First degree relative). The predictive ability of family history was compared to patient age, time from ejaculation, and PSA levels using ROC curves (AUC = 0.55, 0.42, 0.63 respectively). From a literature review, we identified 65miRNAs associatedwith prostate cancer development, transition from indolent to aggressive disease, and metastasis. We found miR-141-3p and miR-376c-3p to be elevated ≥ 1.5-fold in the 17 men with a family history as compared to the 51 men with average risk factors. Further, seven miRNAs were expressed at significantly higher levels in a cohort of 15 prostate cancer patients. Four of these miRNAs are detected at lower levels in cancer-free men, independent of risk status. However, three of these miRNAs (let-7c-3p, miR-130a-5p, miR-221-3p) are not significantly different between men with elevated risk and prostate cancer patients, suggesting a function of these in prostate cancer development and future application as clinical biomarkers. Conclusions: a) Successful establishment of scalable serummiRNAanalysis that allows expression screening between patient populations with different clinical characteristics to discover miRNA signatures. b) Cancer-free men with a family history of prostate cancer have higher levels of miR-141-3p as compared to average risk. Further, miR-141-3p is well established to elevated in the serum of prostate cancer patients and suggests utility as a clinical biomarker to monitor for predicting future cancer development. c) Demonstration of no effect of ejaculation or symptomatic benign prostatic hyperplasia as an indicator of elevated risk from family history. P13 40