Dataset Information

Differential expression of miRNAs involved in biological processes responsible for inflammation and immune response in lichen sclerosus urethral stricture disease.

ABSTRACT:

Purpose

To better understand the pathophysiology of lichen sclerosus (LS) urethral stricture disease (USD), we aimed to investigate expression profiles of microRNAs (miRNAs) in tissue samples from men undergoing urethroplasty.

Methods

Urethral stricture tissue was collected from 2005-2020. Histologic features diagnostic of LS were the basis of pathologic evaluation. Foci of areas diagnostic for LS or non-LS strictures were chosen for RNA evaluation. In an initial screening analysis, 13 LS urethral strictures and 13 non-LS strictures were profiled via miRNA RT-qPCR arrays for 752 unique miRNA. A validation analysis of 23 additional samples (9 LS and 14 non-LS) was performed for 15 miRNAs. Statistical analyses were performed using SPSS v25. Gene Ontology (GO) analysis was performed using DIANA-mirPath v. 3.0.

Results

In the screening analysis 143 miRNAs were detected for all samples. 27 were differentially expressed between the groups (false discovery p-value <0.01). 15 of these miRNAs individually demonstrated an area under the curve (AUC)>0.90 for distinguishing between between LS and non-LS strictures. 11-fold upregulation of MiR-155-5p specifically was found in LS vs. non-LS strictures (p<0.001, AUC = 1.0). In the validation analysis, 13 of the 15 miRNAs tested were confirmed to have differential expression (false discovery p-value <0.10).

Conclusions

To our knowledge this is the first study evaluating miRNA expression profiles in LS and non-LS USD. We identified several miRNAs that are differentially expressed in USD caused by LS vs other etiologies, which could potentially serve as biomarkers of LS USD. The top eight differentially expressed miRNAs have been linked to immune response processes as well as involvement in wound healing, primarily angiogenesis and fibrosis.

SUBMITTER: Kohli H

PROVIDER: S-EPMC8673646 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Urethral stricture is fundamentally a fibrosis of the urethral epithelial and associated corpus spongiosum, which in turn, causes obstruction of the urethral lumen. Patients with urethral stricture most commonly present with lower urinary tract symptoms, urinary retention or urinary tract infection but may also experience a broad spectrum of other signs and symptoms, including genitourinary pain, hematuria, abscess, ejaculatory dysfunction, or renal failure. When urethral stricture is initially suspected based on clinical assessment, cystoscopy is suggested as the modality that most accurately establishes the diagnosis. This recommendation is based on several factors, including the accuracy of cystoscopy, as well as its wide availability, lesser overall cost, and comfort of urologists with this technique. When recurrent urethral stricture is suspected, we suggest performing retrograde urethrography to further stage the length and location of the stricture or referring the patient to a physician with expertise in reconstructive urology. Ultimately, the treatment decision depends on several factors, including the type and acuity of patient symptoms, the presence of complications, prior interventions, and the overall impact of the urethral stricture on the patient's quality of life. Endoscopic treatment, either as dilation or internal urethrotomy, is suggested rather than urethroplasty for the initial treatment of urethral stricture. This recommendation applies to men with undifferentiated urethral stricture and does not apply to trauma-related urethral injuries, penile urethral strictures (hypospadias, lichen sclerosus), or suspected urethral malignancy. In the setting of recurrent urethral stricture, urethroplasty is suggested rather than repeat endoscopic management but this may vary depending on patient preference and impact of the symptoms on the patient.The purpose of this guideline is to provide a practical summary outlining the diagnosis and treatment of urethral stricture in the Canadian setting.