Presentation Authors: Elijah P. Ward, Sarah N. Bartolone, Michael B. Chancellor, Kenneth M. Peters, Laura E. Lamb*, Royal Oak, MI
Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) has elusive etiology, and the lack of understanding of the underlying mechanisms has made clinical diagnosis and treatment challenging. There is also a lack of understanding if IC with Hunner's lesions (HIC) should be considered a separate disease, or if it is the progression of nonulcerative IC (NHIC). In this pilot study, we used mass spectrometry to identify disease-associated proteins in bladder biopsies from patients with IC/BPS with and without Hunner's lesions.
Methods: With IRB approval and patient consent, bladder biopsies were collected from IC/BPS patients with and without Hunner's lesions (N=8). Biopsy samples were digested with trypsin and protein profiles determined using highly sensitive nano Liquid Chromatography with tandem mass spectrometry (nano LC-MS/MS), which identified over 1,700 proteins. Analysis focused on proteins with a p-value less than 0.05 and a fold change greater than 4, and functional pathway analysis was done using the STRING database.
Results: Proteomic analysis of interstitial cystitis bladder samples revealed significant differences in over 147 proteins between bladder tissues of patients with Hunner's lesions versus those without. Pathway analysis for protein-protein interactions of revealed significant increased expression of inflammatory proteins and a decrease in proteins associated with maintaining cellular structure in HIC vs NHIC. There was also a 24X increase in thymidine phosphorylase, suggesting aberrant integrity of blood vessels in HIC bladders.
Conclusions: Bladders of IC/BPS patients with HIC showed significant differences in protein expression when compared to bladders of IC/PBS patients without Hunner's lesions. This included increased inflammation, dysregulation of the cytoskeleton, and aberrant blood vessel integrity. Understanding the signaling networks altered in HIC compared to NHIC will improve identification of biomarkers for classification and help identify novel targeted therapeutics.
Source of Funding: We would like to thank Beaumont Urology and the Taubman family for their generous support of interstitial cystitis research including this project.