Meta-analysis of differentially expressed microRNAs in systemic sclerosis

Abstract

Objective: Emerging evidence suggests a possible role of microRNAs (miRNAs) that can regulate gene expression in the pathogenesis of systemic sclerosis (SSc). However, contradictory results have been reported on miRNA expression in SSc. We performed a meta-analysis to identify the consistently differentially expressed miRNAs in SSc across studies.

Methods: We performed a systematic search in PubMed using the terms "microRNAs OR Circulating MicroRNA OR miRNAs" AND "systemic sclerosis OR systemic scleroderma" to identify full-text English publications until 1 August, 2019. After quality assessment using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), we utilized RevMan 5.3 and Meta-Disc 1.4 to assess heterogeneity (I² index and Q test P values) and perform effect size modeling.

Results: From 120 publications in the initial search, 16 studies on miRNA expression profiles in blood and/or dermal fibroblasts were selected after publication screening. The median number of samples in these studies was 36 (interquartile range 19-59, range 10-119). Meta-analysis revealed 8 differentially expressed miRNAs, of which miR-21 in blood, miR-29a, miR-155, and miR-196a in dermal fibroblasts, and let-7a in both serum and dermal fibroblast samples were most consistent across studies. These miRNAs have been implicated in immune activation, vascular damage, and fibroblast activation, which could potentially lead to the overproduction of collagen and extracellular protein.

Conclusion: Studies of miRNA expression in SSc are limited and have used a relatively small number of samples. A meta-analysis of these reports reveals a cluster of differentially expressed miRNAs implicated in immune activation, vascular damage, and fibroblast activation that could play roles in SSc pathogenesis and serve as potential biomarkers.

Keywords: autoimmune disease; epigenetics; meta-analysis; miRNA; systemic sclerosis.