Open Access

ARTICLE

Functional genomic analyses of IC/BPS patient subgroups: a pilot study

Tyler Overholt^1,2, Robert J. Evans¹, Gopal Badlani¹, Catherine A. Matthews¹, Stephen J. Walker^1,2

1 Department of Urology/Female Pelvic Health, Wake Forest Baptist Medical Center, Winston Salem, North Carolina, USA
2 Wake Forest Institute for Regenerative Medicine, Winston Salem, North Carolina, USA
Address correspondence to Dr. Stephen J Walker, Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston Salem, NC 27101 USA

Canadian Journal of Urology 2022, 29(1), 11012-11019.

Abstract

Introduction: To further facilitate understanding of disease pathophysiology and patient stratification in interstitial cystitis/bladder pain syndrome (IC/BPS), we utilized molecular phenotyping to compare three clinically distinct IC/BPS patient subgroups.
Materials and methods: Total RNA (miRNA and mRNA) was isolated via standard protocols from IC/BPS patient bladder biopsies and assayed on whole genome and microRNA expression arrays. Data from three patient subgroups (n = 4 per group): (1) low bladder capacity (BC; ≤ 400 cc) without Hunner’s lesion, (2) low BC with Hunner’s lesion, and (3) non-low BC (> 400 cc) were used in comparative analyses to evaluate the influence of BC and HL on gene expression profiles in IC/BPS.
Results: The BC comparison (Group 1 v 3) identified 54 miRNAs and 744 mRNAs. Eleven miRNAs mapped to 40 genes. Hierarchical clustering of miRNA revealed two primary clusters: (1) 3/4 low BC patients; (2) 4/4 non-low and 1/4 low BC patients. Clustering of mRNA provided clear separation based on BC. The HL comparison (Group 1 v 2) identified 16 miRNAs and 917 mRNAs. 4 miRNAs mapped to 13 genes. Clustering of miRNA and mRNA revealed clear separation based on HL status.
Conclusions: Significant molecular differences in IC/BPS were found to be associated with the low BC phenotype (e.g., an upregulation of cell proliferation and inflammation marker genes), as well as additional molecular findings that further define the HL+ phenotype (e.g., upregulation of genes involved in bioenergetics reactions) and suggest oxidative stress may play a role.

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