Candidate microRNA Biomarkers in Lupus Nephritis: A Meta-Analysis of Profiling Studies in Kidney, Blood and Urine Samples

Abstract

Lupus nephritis (LN) is a kidney disease caused by systemic lupus erythematosus in which kidneys are attacked by the immune system. MiRNAs participate in the pathogenesis of LN as modulatory effectors in immune responses and nephrogenesis pathways. Despite the large number of miRNAs that are expressed deferentially, identifying the most suitable biomarker candidate for LN is challenging. The aim of this study was to introduce a consensus panel of potential miRNA biomarkers by performing a meta-analysis of miRNA profiles in the kidney, blood, and urine samples of LN patients. A comprehensive literature review approach was considered to find LN-related miRNA expression profiles. After including the 41 eligible studies and performing the data extraction, meta-analysis was done based on the vote-counting rank strategy and as well as meta-analysis of p-value. The result of the meta-analysis was three lists of consensus miRNAs with altered expression profiles in the various tissue samples of LN patients. Of the 13 studies on kidney tissue, the meta-miRNAs were let-7a, miR-198, let-7e, miR-145, and miR-26a. In addition, meta-miRNAs of miR-199a, miR-21, miR-423, miR-1260b, miR-589, miR-150, miR-155, miR-146a, and miR-183 from 21 studies on blood samples, and miR-146a, miR-204, miR-30c, miR-3201, and miR-1273e from 11 studies on urine samples can be considered as non-invasive biomarker panels for LN. The meta-miRNAs and their related genes were subjected to functional enrichment analyses and network construction. Functional enrichment analysis confirmed the involvement of their target genes in nephropathy-related signaling pathways. Network construction showed miR-145-5p in blood and miR-155-5p in kidney, the best hob miRNAs as candidate drug targets. In conclusion using a meta-analysis approach, our study proposes three meta-miRNA panels that could be the target of further research to assess their potential as biomarkers / therapeutic targets in LN disease.