Abstracts from the New England Section of the AUA 2021

NE-AUA 2021 Abstracts P9 WITHDRAWN P10 The Impact of the COVID-19 Pandemic on Online Interest in Urologic Conditions Michael Rezaee, MD, MPH , Amanda Swanton, MD, PhD, Martin Gross, MD Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA Introduction: The effects of the COVID-19 pandemic on urologic care are only beginning to be understood. Search engines can be used to track public interest in health conditions and evaluate how this interest changes in response to major societal events. We aimed to examine trends in online search behaviors related to benign and malignant urologic conditions during the COVID-19 pandemic using a major search engine. Materials &Methods: Google Trends was queried using the terms prostate cancer, bladder cancer, kidney cancer, urinary incontinence (UI), kidney stone, erectile dysfunction (ED), peyronies disease (PD), benign prostate hyperplasia (BPH), infertility, and vasectomy between January 2019 and February 2021. Search volume index (SVI), a measure of relative search volume on Google, was obtained for each search term and examined by time period: prior to widespread public knowledge of COVID-19 (January 2019 - January 2020) and during the height of the COVID-19 pandemic in the United States (February 2020 - February 2021). Results: Online interest in urologic malignancies decreased during the COVID-19 pandemic. Average SVI for prostate cancer (87.7 vs. 77.6, p<0.001), bladder cancer (74.0 vs. 65.7, p<0.001), and kidney cancer (62.2 vs. 54.1, p<0.001) significantly decreased over time. Average SVI for benign urologic conditions, includingUI (80.2 vs. 77.6, p=0.09), BPH (79.6 vs. 78.8, p=0.67), ED (49.8 vs. 47.2, p=0.12) and PD (47.7 vs. 42.8, p=0.16) did not change during the pandemic, with the exception of kidney stones which decreased (86.4 vs. 82.6, p=0.02). Online interest in infertility significantly increased during the pandemic (52.2 vs. 57.3, p=0.01), while interest in vasectomies decreased (49.8 vs. 44.6, p<0.01). Conclusions: Online interest in urologic malignancies was differentially impacted by the COVID-19 pandemic, which raises significant questions about the potential effects on cancer patients. The pandemic had no effect on online interest in benign urologic conditions. Infertility was the only condition that experienced an increase in online interest during the pandemic. P11 The Expression of Estrogen Receptors is Associated with Steroid 5-alpha Reductase 2 in Prostatic Tissue Christina Sharkey, MLA , Xingbo Long, MD, Aria F. Olumi, MD, Zongwei Wang, PhD Beth Israel Deaconess Medical Center, Boston, MA, USA Introduction: Benign prostatic hyperplasia (BPH) is a highly prevalent health problem among elderly men. Steroid 5 α reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic development and growth. However, patients respond very differently to 5 α -reductase inhibitors (5ARIs). Our previous study demonstrated an “androgenic to estrogenic switch” when SRD5A2 is absent in the prostate gland. Here we wished to identify if estrogen receptors (ER) expression is associatedwith SRD5A2 in the prostate. Materials & Methods: 18 prostatic specimens collected from patients who underwent transurethral resection of the prostate were used to determine the transcript and protein expressions of ER α and ER β. Mouse and human single-cell RNA sequencing (scRNA seq) data were analyzed to identify the subpopulation for ER α and ER β expression. The expression of ERs was correlated to SRD5A2 expression with RNA sequencing (RNA seq) data from GTEx (Genotype-Tissue Expression, n=100) in normal prostate and TCGA (The Cancer Genome Atlas, n=496) databases for prostate cancer. Human prostatic stromal cell line (BHPrS1) and epithelial cell line (BPH1) were transfected with SRD5A2 plasmid or vector to identify the c hange of transcript and protein levels of SRD5A2, ER α , and ER β. Results: ER α and ER β variably expressed in both the stroma and epithelium compartments of BPH surgical samples and had nucleus expression in human prostatic cell lines. ScRNAseq analysis of human and mouse prostate tissues showed that SRD5A2 is dominantly expressed in fibroblasts. Meanwhile, ER α expressed mainly in myofibroblasts of the human prostate and luminal cells of the mouse anterior prostate. ER α had minimal expression both in mouse and human prostate. RNA seq analysis demonstrated a significant association between SRD5A2 and ER α in human benign and malignant prostate tissue. The transcript level of SRD5A2 was significantly positively correlated with ER β (R=0.6797, p=0.0019) and ER α (R=0.7030, p=0.0011) in surgical specimens. In addition, in BHPrS1 cells, transcript and protein expressions of total ER α and phosphorylated ER β were upregulated in SRD5A2 overexpressed cells compared with vector control. Conclusions: Our study demonstrates that the expression of ER α is associated with SRD5A2 expression. Targeting the estrogenic signaling pathway may serve as an effective treatment strategy in 5ARI-insensitive BPH patients. Concurrent Poster Session I Single Cell Sequencing Reveals Luminal Epithelial Plasticity with Fibroblast Activation Upon SRD5A2 Deletion in the Prostate Christina Sharkey, MLA , Xingbo Long, MD, Zongwei Wang, PhD, Aria F. Olumi, MD Beth Israel Deaconess Medical Center, Boston, MA, USA Introduction: Steroid 5 α reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic development and growth. SRD5A2 inhibitors are the only class of benign prostate hyperplasia-relatedmedications that reduce prostate size. However, patients respond variably to 5ARI therapies. Due to epigenetic modifications, we have previously demonstrated that 30% of adult human prostatic tissues do not express the SRD5A2 gene and protein. The goal of this study is to use single cell RNAsequencing (scRNAseq) to characterize the prostate cellular and transcriptomic changes when SRD5A2 is absent. Materials & Methods: Homozygous SRD5A2-/- mice and littermate heterozygous SRD5A2+/- control mice were generated. The intact prostate tissues were collected from 8-16 weeks old mice and digested for single cells. ScRNAseqwith 10x genomics platform, followed by unsupervised clustering, was utilized to generate cell clusters based on differentially expressed (DE) gene profiles. A complete transcriptomic profile was obtained to identify cellular subsets and functional differentiation. Results: ScRNA seq resulted in transcriptome data for clustering of 23,000 single cells, whichwere further annotated to 18 subpopulations demonstrating the heterogeneity within prostate. The SRD5A2 gene was identified to exclusively express in fibroblasts and myofibroblasts. Deletion of SRD5A2 induced a significant decrease of epithelial luminal cells (53.2% vs. 31.8%), while there was a significant elevation of stromal (11.3% vs. 18.0%) and immune cells (3% vs. 6.6%). Further sub-clustering of luminal cells identified 3 unique subclusters with gene signature of lineage, estrogen and progenitor pathways. Luminal cells with lineage signature and progenitor signature diminished whereas luminal cells with estrogen signature stably survived after SRD5A2 knock down. Meanwhile, cell-cell communication analysis showed that fibroblasts have broad ligand/receptor interactions with other cell types. In particular, fibroblasts support the epithelial proliferation and immune cells recruitment of prostate through secretion of growth factors (EGF, FGF and IGF families) and cytokines (CXCL, CCL and HLA). More importantly, absence of SRD5A2 in fibroblasts exhibited significantly increased expression patterns of inflammatory, epithelial-mesenchymal transition and angiogenesis genes. Conclusions: Our data suggests that luminal cells with the signature of estrogen response gene, and fibroblasts that have the enhanced function may synergistically contribute to 5ARI treatment resistance. Understanding the mechanism(s) by which prostatic fibroblasts regulate development of epithelial luminal cells may pave the way to find new therapeutic targets to the management of BPH patients who lack of SRD5A2 expression and are potentially resistant to 5ARI. P12 WITHDRAWN P8 39