Spatial MicroRNA Expression in Lichen Sclerosus Induced Urethral Strictures
Anna Saltman, MD, MS1, Aaron Perecman, MD1, Travis Sullivan, MS1, Eric Burks, MD2, Myrtha Constant, n/a2, Kim Reiger-Christ, PhD1, Alex Vanni, MD1.
1Lahey Hospital and Medical Center, Burlington, MA, USA, 2Boston Medical Center, Boston, MA, USA.
BACKGROUND: Lichen sclerosus (LS) is an inflammatory disease of the genital skin that has been linked to urethral stricture disease (USD). LS strictures tend to be longer and are more likely to recur. Little is known about the underlying pathophysiology of this disease. MicroRNAs are small, non-coding segments of RNA that control gene expression by binding to mRNA. Previous studies have shown differential miRNA expression between LS and non-LS USD. We aim to use in situ hybridization (ISH) to evaluate spatial expression of these miRNA between LS and non-LS strictures.METHODS: Four miRNAs (miR-142, miR146a, miR-150, and miR155) were selected for analysis from a pilot study of 8 up-regulated miRNAs. ISH staining was done on tissue microarrays of 2mm punches consisting of 29 non-LS & 17 LS strictures. Five (5) micron sections were stained using heat induced epitope retrieval with miRNAscope HD reagents (ACDBio, Newark, CA). Mucosal and submucosal probe detection was scored using QuPath software. Continuous variables were evaluated using the Mann-Whitney U test and categorical variables were evaluated using the Chi-squared test, with SPSS v.28.RESULTS: There was a significant difference in the expression of submucosal miR-155 between LS and non-LS tissue (0.44 vs 0.07, respectively, p = 0.002). No significant difference was seen for the submucosa of miR-142, miR-146a, miR-150, or the mucosal tissue for any of the miRNAs. A significant difference was seen in the number of patients that had lymphocyte-dense tissue between LS and non-LS submucosa (70.6% vs. 27.6%, respectively, p = 0.005).CONCLUSIONS: In previous studies we have shown that there is an overall up-regulation of miR-142, miR-146a, miR-150, and miR-155 in the tissue of LS strictures, but with ISH have shown that only miR-155 has a differential spatial expression, prominent significantly in the submucosa. More research is needed to determine the significance of this up-regulation and determine its role in the diagnosis, prognosis, and therapy for LS strictures.
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