MP07-01 MICRORNA EXPRESSION PROFILE ANALYSIS OF PHENOTYPICALLY DISTINCT INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME PATIENTS

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (MP07)1 Apr 2020MP07-01 MICRORNA EXPRESSION PROFILE ANALYSIS OF PHENOTYPICALLY DISTINCT INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME PATIENTS Tyler Overholt*, Robert Evans, Catherine Matthews, Gopal Badlani, Trang Simon, and Stephen Walker Tyler Overholt*Tyler Overholt* More articles by this author , Robert EvansRobert Evans More articles by this author , Catherine MatthewsCatherine Matthews More articles by this author , Gopal BadlaniGopal Badlani More articles by this author , Trang SimonTrang Simon More articles by this author , and Stephen WalkerStephen Walker More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000827.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pelvic condition with unclear pathophysiology. Identification of patient subgroups would be clinically useful for addressing diagnosis and management challenges. Using anesthetic bladder capacity (BC) as a clinical delineator, we previously investigated gene expression profile differences in IC/BPS patient bladder biopsy samples and found that patients with low BC (≤400cc) had a significantly different expression profile than patients with non-low BC (>400cc). Herein, we extend these findings by adding microRNA analyses. METHODS: Bladder biopsies were selected from our biorepository of IC/BPS patient samples to represent three clinical subgroups: Group A: low BC; Group B: low BC with Hunners lesion (HL+), Group C: non-low BC. Total RNA (mRNA and miRNA) was isolated via standard protocols and assayed on whole genome and miRNA expression arrays. Differential expression analyses were conducted between: [1] Groups A & C (low vs non-low BC) and [2] Groups A & B (HL+ vs HL-). RESULTS: Comparison #1 identified 744 differentially expressed transcripts (DETs; p<0.01) and 54 differentially expressed miRNAs (p<0.05). Using Ingenuity Pathway Analysis (IPA) software, 11 miRNAs mapped to 40 genes. Hierarchical clustering of miRNA revealed two primary clusters (Figure 1A): one cluster consisted of entirely low BC patients and a second cluster consisted of 4 non-low and 1 low BC patients. Comparison #2 identified 917 DETs (p<0.01) and 16 miRNAs (p<0.05); 4 miRNAs mapped to 13 genes. Hierarchical clustering of miRNA revealed a clear separation of samples based on HL status (Figure 1B). CONCLUSIONS: In Comparison #1, upregulated genes were over-represented in cell proliferation and inflammation pathways, suggesting potential biological themes for the low BC phenotype. In addition to over-representation of these same pathways in Comparison #2, upregulated genes were also over-represented in oxidation-reduction pathways, suggesting in addition to inflammation and abnormal cell proliferation, oxidative stress may underlie the HL+ phenotype. This study identified significant molecular differences in IC/BPS associated with low vs non-low BC phenotype, and additional molecular findings that further define the HL+ phenotype. Source of Funding: NIH R21 DK106554-01 (SJW) © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e95-e95 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tyler Overholt* More articles by this author Robert Evans More articles by this author Catherine Matthews More articles by this author Gopal Badlani More articles by this author Trang Simon More articles by this author Stephen Walker More articles by this author Expand All Advertisement PDF downloadLoading ...