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 pro les in the kidney, blood, and urine samples of LN patients. A comprehensive literature review approach was considered to nd LN-related miRNA expression pro les. After including the 41 eligible studies and performing the data extraction, metaanalysis 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 pro les 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 con rmed 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.

A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases

“…However, recent statistical approaches have made it possible to combine miRNA profiling studies from different platforms without raw data and generalized normalization using RRA [ 20 , 73 ] and the vote-counting method [ 21 ]. These approaches have been successfully validated in previous studies in kidney diseases [ 13 , 15 , 17 ] and heart failure [ 22 ]. Our meta-analysis summarizes hypothesis-free miRNA profiling studies of CKDs by etiology, biological samples, and stages that might reveal novel miRNAs and avoid miRNA selection bias from the investigator side.…”

“…Studies have identified dysregulation of miRNA in various types of kidney diseases in mice [ 10 , 13 ] and humans [ 14 , 15 , 16 , 17 ], suggesting their use as potential biomarkers for diagnosis [ 18 ] and as nucleic acid therapy [ 19 ]. Therefore, it is crucial to understand the miRNA expression patterns in various sample types during specific disease stages and their functional role in the development and progression of CKD.…”

“…Recently, novel statistical methods, Robust Rank Aggregation (RRA) and vote-counting, implemented by researchers have provided a possibility to integrate miRNA lists from different platforms, such as gene sequencing, microarray, and RT-qPCR, without being affected by cut-off and normalization methods and complete raw data [ 20 , 21 ]. These methods have been used in previous meta-analyses in diabetic nephropathy, lupus nephritis, renal fibrosis [ 13 , 15 , 17 ], and heart failure [ 22 ].…”

Lupus Nephritis Biomarkers: A Critical Review

“…Several miRNAs serve as potential disease biomarkers for LN. Epigenetic studies regarding SLE have highlighted a set of urinary miRNAs, including miR-146a, miR-204, miR-30c, miR-3201, and miR-1273e, that are associated with LN [125]. These miRNAs play roles in LN-specific pathways, such as nucleic acid processes and inflammation, as well as in kidney function regulation through WNT and TGF-β signaling.…”

Lupus Nephritis Risk Factors and Biomarkers: An Update

“…Among epigenetic alterations reported in SLE, a list of 5 urinary miRNAs (miR-146a, miR-204, miR-30c, miR-3201, miR-1273e) present in extracellular vesicles have been associated with LN in a meta-analysis from 11 LN studies [127]. These miRNAs are associated with LN-related pathways (e.g., RNA/DNA nucleic acid and inflammatory pathways) and renal homeostasis (e.g., WNT and TGF-beta signaling).…”