MP35-13 NEUROINFLAMMATORY GENE EXPRESSION IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS): INSIGHTS INTO ETIOLOGY AND PHENOTYPE BIOLOGY

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia (MP35)1 Sep 2021MP35-13 NEUROINFLAMMATORY GENE EXPRESSION IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS): INSIGHTS INTO ETIOLOGY AND PHENOTYPE BIOLOGY Johnathan Doolittle, Karen Keslar, Paige Gotwald, Sarah Vij, and Daniel Shoskes Johnathan DoolittleJohnathan Doolittle More articles by this author , Karen KeslarKaren Keslar More articles by this author , Paige GotwaldPaige Gotwald More articles by this author , Sarah VijSarah Vij More articles by this author , and Daniel ShoskesDaniel Shoskes More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002044.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: CP/CPPS has diverse clinical phenotypes and its etiology is multifactorial with inflammatory, immune and neuromuscular pathways implicated. Studies to date of gene expression in humans have been limited to small numbers of target genes. NanoString uses barcoded probes to simultaneously measure hundreds of genes. We wished to study gene expression in blood and urine of CP/CPPS patients compared to controls for a broad variety of neuroinflammatory genes and characterize the results by patient phenotype. METHODS: Blood and urine were collected from 10 men with CP/CPPS and 7 asymptomatic controls. RNA was isolated from urine pellets using Qiagen RNeasy kits. Whole blood was collected and RNA isolated using the Tempus Spin RNA isolation kit. 100 ng of RNA was used for gene expression analysis with the 770-gene NanoString Human Neuroinflammation gene panel. Data was imported into Rosalind (OnRamp Bioinformatics) for normalization, calculation of fold-changes and p values, and identification of enriched pathways. Gene expression was considered significantly different if there was a greater than 1.5x change compared to controls and corrected p was <0.05. RESULTS: Mean patient age was 42.2 years, median symptom duration was 15.5 months, median UPOINT domains was 3 and mean total NIH-CPSI score was 28.8. In blood, there were 5 genes with significantly different expression to controls, the largest differences found in FOS1 (neuropathic pain control), PROS1 (blood clotting and found in prostate cancer cells) and DDX58 (antiviral innate immunity). Gene set analysis showed differences in inflammation, angiogenesis and cytokine signaling. In urine there were 48 genes with significantly different expression including SLAMF8 (CD2 mediated lymphocyte activation) and LAIR1 (inhibits B and T cell function). Gene set analysis showed differences in Wnt (adaptive immune response in neuropathic pain), microglial function and inflammatory signaling. Subgroup analysis by UPOINT domain showed unique gene expression in the Psychosocial, Organ Specific and Neurologic/Systemic domains in both blood and urine for neurogenic pain and cytokine signaling associated genes. CONCLUSIONS: Men with CP/CPPS have a diverse set of neuroinflammatory genes with differential expression compared to controls including some never before implicated in the etiology of this condition. Furthermore, clinical phenotypes have distinct patterns of gene expression. These findings could lead to novel biomarker development, novel treatment options and further validates the biologic basic of clinical phenotyping. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e632-e632 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Johnathan Doolittle More articles by this author Karen Keslar More articles by this author Paige Gotwald More articles by this author Sarah Vij More articles by this author Daniel Shoskes More articles by this author Expand All Advertisement Loading ...