Presentation Authors: Stephen Walker*, Jeffrey Schachar, Gopal Badlani, Catherine Matthews, Joao Zambon, Robert Evans, Winston Salem, NC
Introduction: The goal of this study was to further explore our working hypothesis that the low capacity bladder mucosal gene expression profile is representative of a bladder-centric interstitial cystitis/bladder pain syndrome (IC/BPS) sub-phenotype. This hypothesis is based on data from our earlier pilot study showing that a subset of IC/BPS patients (those with a severely diminished bladder capacity [BC; â‰¤400 ml]) displayed a unique gene expression profile.
Methods: IC/BPS patient biopsy samples (N=40) were selected from our tissue bank (IRB00018552) for gene expression profiling. Specimens were chosen based on anesthetic bladder capacity (BC) ranging from 200-1500ml to provide a representative sample of the entire cohort. Thirteen samples came from patients that we define as &[prime]low&[prime] BC (≤400 ml; 7/13 were Hunner&[prime]s lesion positive [HL+]) and 27 were from patients with a BC >400 ml (1/27 was HL+). All patients had undergone therapeutic bladder hydrodistention per the AUA guideline algorithm. Total RNA was isolated from mucosal biopsies (per standard protocols) and assayed on whole genome microarrays (Illumina HT v4 BeadArray). Hierarchical clustering was used to identify similar groups of samples on the basis of their gene expression profile.
Results: Bladder capacity accounted for approximately 60% of the overall variation in mucosal gene expression among all samples. Hierarchical clustering revealed two primary clusters (Figure 1). Cluster A consisted exclusively of samples from the BC >400ml group (heatmap; Figure 1, right side). Cluster B contained all samples with BC â‰¤400 ml (Figure 1, left side). Within Cluster B there are 2 sub-groups: one consisting largely of low BC /HL+ samples; the other consisting largely of those with low BC/HL-. Four of the 5 samples that were not in the &[prime]low&[prime] BC group and yet clustered within the &[prime]low&[prime] BC/HL- subgroup had diminished BC (either 450 or 500 ml).
Conclusions: Gene expression in mucosal biopsy tissue from IC/BPS patients provides a degree of stratification when correlated with anesthetic bladder capacity. These pilot data reveal three distinct IC/BPS subgroups and information mined from differentially-expressed genes between each subgroup may provide further insight into the heterogeneity seen in IC/BPS.
Source of Funding: NIH NIDDK R01 (SJW)