LAUSR

INTRODUCTION AND OBJECTIVE: The pathophysiology of Lichen Sclerosus (LS) urethral stricture disease (USD) is poorly understood. MicroRNA (miRNA) are non-coding genetic material involved in the regulation of gene expression. We sought to examine the pathophysiology of LS and non-LS USD by comparing miRNA expression profiles in men undergoing urethroplasty. METHODS: Total RNA was extracted from formalin-fixed, paraffin-embedded tissue samples from 13 LS urethral strictures and 13 non-LS urethral strictures collected from 2005-2017. The pathologic evaluation of strictures was based on histologic features considered diagnostic of LS. Representative portions of the FFPE block containing diagnostic foci of LS or non-LS strictures were selected by the pathologist for molecular evaluation. Each of these samples was profiled via miRNA RT-qPCR arrays for 752 unique miRNA. Statistical analyses were performed using SPSS v25. RESULTS: There were no significant differences regarding patient age, BMI, smoking history, or medical comorbidities between the LS vs nonLS groups. Of the 181 miRNA detected for all samples, 18 were differentially expressed between the groups (false discovery p-value <0.01; Figure 1a). 14 of these miRNA each achieved an area under the curve (AUC)>0.90 for discriminating between LS and non-LS strictures. Principal components analysis demonstrated distinct grouping of the LS and non-LS samples (Figure 1b). MiR-155-5p specifically was found to upregulated by 11 fold in LS vs. non-LS strictures (p<0.001, AUC[1.0). CONCLUSIONS: To our knowledge this is a novel investigation into the pathophysiology of LS USD; no existing studies have evaluated the miRNA expression profiles in LS and non-LS USD. We have identified 18 distinct miRNA that differentiate USD caused by LS vs other etiologies. These miRNA have been linked to gene expression in pathways responsible for autoimmunity, systemic sclerosis, cell proliferation, apoptosis, and angiogenesis. Further investigation is needed to evaluate the gene expression pathways associated with USD.