Abstract: PD01-06
Sources of Funding: _x000D_ Interstitial Cystitis Association Pilot Research Program Grant _x000D_ R21DK106554-01 (NIDDK)

Introduction

The goal of this study was to test the hypothesis that the low capacity (≤ 400 ml) bladder mucosal gene expression profile represents a bladder-centric IC/BPS sub-phenotype. This hypothesis is based on data from our previously reported pilot study showing that a subset of IC/BPS patients (those with a severely diminished bladder capacity {BC; ≤ 400 ml}) displayed a unique gene expression profile.

Methods

Selection of female IC/BPS patient biopsy samples from our tissue bank (IRB00018552) for gene expression profiling was made on the basis of anesthetic bladder capacity. All patients had undergone therapeutic bladder hydrodistention per the AUA guideline algorithm. There were 3 groups: (1) low capacity group (BC ≤ 400 ml; N=13), (2) BC between 450-1500 ml (N=28) and, (3) control group (non-IC/BPS patients undergoing a pelvic reconstruction procedure; N=7). Total RNA was isolated from mucosal biopsies (per standard protocols) and assayed on whole genome microarrays (Illumina HT v4 BeadArray).

Results

Mucosal gene expression profiles differ significantly between controls and IC/BPS patients (Figure 1A). Key differences in the Epithelial Adherens Junction Signaling pathway were apparent (p = 5.14E-05) between these two groups. Among only IC/BPS patients, gene expression profiles were also significantly different between those with a low capacity compared to those with BC > 400 (Figure 1B). One striking pathway impacted in this comparison was the EIF2 Signaling (eukaryotic translation initiation factor) pathway (p = 8.2E-26). Finally, gene expression profiles in the low BC group with Hunner&[prime]s lesions were significantly different from those without lesions (Figure 1C). Not surprisingly, differential expression analysis produced inflammatory disease (p = 1.46E-9) as a top classifier in this group comparison.

Conclusions

Mucosal gene expression in low anesthetized bladder capacity patients is distinct from gene expression profiles in higher capacity samples and from controls. These findings suggest low BC patients, with or without Hunner&[prime]s lesions, represent a sub-phenotype of IC/BPS and these gene expression differences, if confirmed, may yield additional therapeutic targets for this bladder-centric phenotype.

Funding

_x000D_ Interstitial Cystitis Association Pilot Research Program Grant _x000D_ R21DK106554-01 (NIDDK)