Circulating miRNA-181b-5p, miRNA-223-3p, miRNA-210-3p, let 7i-5p, miRNA-21-5p and miRNA-29a-3p in patients with localized scleroderma as potential biomarkers

Abstract

Localized scleroderma (LoSc) is a rare disease manifested by an inflammation and sclerosis of the skin. The latest studies focused on glycoprotein Krebs von den Lungen-6, surfactant protein-D, chemokine ligand 18 and dipeptidylpeptidase 4 as potential biomarkers of skin fibrosis in systemic scleroderma. Our study aimed to identify 6 miRNAs with elevated or decreased levels in 38 LoSc patients (31 females, 7 males) compared to healthy volunteers (HVs) and to correlate the selected miRNAs' serum levels with the severity and the clinical symptoms of LoSc and some laboratory parameters with the selected miRNAs' serum levels. The serum levels of miRNAs, i.e. miRNA-181b-5p, miRNA-223-3p, miRNA-21-5p, let 7i-5p, miRNA-29a-3p and miRNA-210-3p were significantly increased in the LoSc patients compared to the HVs. The level of let-7i increase in the female LoSc patients correlated negatively with BSA (r = - 0.355, p = 0.049) and mLoSSI (r = - 0.432, p = 0.015). Moreover, the female patients with inactive LoSc had significantly higher level of let-7i (2.68-fold on average) in comparison to those with active disease (p = 0.045). The exact role of those molecules has not been revealed in LoSc and a long-term longitudinal research is pivotal to confirm their prognostic value.

Figure 1

The strategy of miRNAs selection in our study.

Figure 2

miRNAs’ relative fold change (2^−ΔΔCt) in all localized scleroderma patients compared to healthy volunteers (a) and in female localized scleroderma patients compared to healthy volunteers (b). p for Mann–Whitney’s test, LoSc localized scleroderma, IQR interquartile range.

Figure 3

Relative fold change (2^−ΔΔCt) of let-7i-5p versus BSA (a) and mLoSSI (b) in female localized scleroderma patients. r Spearman’s correlation coefficient, BSA body surface area, mLoSSI modified Localized Scleroderma Skin Severity Index.

Figure 4

Statistically significant correlations between miRNAs’ relative fold change (2^−ΔΔCt) and clinical characteristics of the female localized scleroderma patients. (a) Relative fold change in patients versus healthy volunteers. (b) Relative fold change in patients compared between two groups. p for Mann–Whitney’s test, IQR interquartile range, LoSc localized scleroderma, CRP C-reactive protein, RF rheumatoid factor, EPwS erythematous patches without sclerosis, ADs concurrent autoimmune diseases.

Figure 5

Enrichment analysis. (A) The KEGG pathway analysis of hsa-181b-5p; (B) the KEGG pathway analysis of hsa-miR-223-3p; (C) the KEGG pathway analysis of hsa-210-3p; (D) the KEGG pathway analysis of hsa-let-7i-5p; (E) the KEGG pathway analysis of hasmiR-21-5p; (F) the KEGG pathway analysis of hsa-29a-3p. The enrichment score is expressed as –log (p value)^–.