MicroRNAs in Colon Tissue of Pediatric Ulcerative Pancolitis Patients Allow Detection and Prognostic Stratification

Abstract

Prevalence of inflammatory bowel disease has been on the rise in recent years, especially in pediatric populations. This study aimed to provide precise identification and stratification of pediatric patients with diagnosed ulcerative colitis (UC) according to the severity of their condition and the prediction for standard treatment according to the specific expression of candidate miRNAs. We enrolled consecutive, therapeutically naïve, pediatric UC patients with confirmed pancolitis. We examined formalin-fixed paraffin-embedded specimens of colonic tissue for the expression of 10 selected candidate miRNAs. We performed receiver operating characteristic curve analysis, using area under the curve and a logistic regression model to evaluate the diagnostic and predictive power of the miRNA panels. Sixty patients were included in the final analysis. As a control group, 18 children without macroscopic and microscopic signs of inflammatory bowel disease were examined. The combination of three candidate miRNAs (let-7i-5p, miR-223-3p and miR-4284) enabled accurate detection of pediatric UC patients and controls. A panel of four candidate miRNAs (miR-375-3p, miR-146a-5p, miR-223-3p and miR-200b-3p) was associated with severity of UC in pediatric patients and a combination of three miRNAs (miR-21-5p, miR-192-5p and miR-194-5p) was associated with early relapse of the disease. Nine patients out of the total were diagnosed with primary sclerosing cholangitis (PSC) simultaneously with ulcerative colitis. A panel of 6 candidate miRNAs (miR-142-3p, miR-146a-5p, miR-223-3p, let-7i-5p, miR-192-5p and miR-194-5p) identified those patients with PSC. Specific combinations of miRNAs are promising tools for potential use in precise disease identification and severity and prognostic stratification in pediatric patients with ulcerative pancolitis.

miRNA-Based Potential Biomarkers and New Molecular Insights in Ulcerative Colitis

“…At present, miRNA biomarkers in UC are mainly studied for clinical diagnosis and monitoring, however, miRNA biomarkers seem to have other values. Due to the broad regulatory effects of miRNA, it is associated with almost all clinical reactions, such as in predicting disease recurrence (Jabandziev et al, 2021), therapeutic escalation (Kalla et al, 2020), and response to drug therapy (Batra et al, 2020). Although this aspect is currently under-researched, they do represent a valuable direction of research.…”

“…Similarly, Morilla et al used a panel of miRNA biomarkers (has-miR-3934, hsa-miR-100, hsa-miR-718, hsa-miR-193b, hsa-miR-3150a-5p, hsa-miR-1260b, hsa-miR-938, has-miR-518b, andhsa-miR-1468) to distinguish steroidresistant acute severe ulcerative colitis (ASUC) patients with high accuracy (AUC 0.87) (Morilla et al, 2019). Jabandziev et al analyzed miRNA expression in colonic tissue of 60 pediatric UC patients and found four panels of miRNAs, which were used to distinguish pediatric UC patients from healthy controls AUC 0.99), to detect severity in pediatric UC patients ACU 0.73), to detect disease relapse within one year of treatment AUC 0.73) and to diagnose UC patients with primary sclerosing cholangitis (miR-142-3p, miR-146a-5p, miR-223-3p, let-7i-5p, miR-192-5p and miR-194-5p, AUC 0.858) (Jabandziev et al, 2021).…”

Long non-coding RNA SNHG5 regulates ulcerative colitis via microRNA-375 / Janus kinase-2 axis

“…miR-375 was predicted and proved to be a target miRNA of SNHG5. miR-375 was evidenced to be down-regulated in UC [ 28 , 29 ]. It is down-regulation activated inflammatory signaling in UC [ 28 ].…”

“…Dysregulated miR-375 contributes to the progression of oral squamous cell carcinoma [ 24 ], prostate cancer [ 25 ], CRC [ 26 ], and osteosarcoma [ 27 ]. Furthermore, miR-375 was down-regulated in UC [ 28 , 29 ]. In this study, the potential roles of SNHG5 and miR-375 in UC were investigated.…”

lncRNA PVT1 in the Pathogenesis and Clinical Management of Renal Cell Carcinoma

“…With the development of targeted therapy, more attention has been turned to predictive biomarkers [ 6 ]. However, there is currently no biomarker reaching a sufficient specificity and sensitivity enabling the precise personalization of the therapy [ 5 ], although great scientific effort has been focused on searching for biomarkers in many human diseases [ 7 ], including RCC [ 5 ]. Among the potential molecules feasible as biomarkers, long non-coding RNAs have been studied excessively.…”