Serum Based miRNA as a Diagnostic Biomarker for Multiple Sclerosis: a Systematic Review and Meta-Analysis

Abstract

This systematic review and meta-analysis aimed to identify deferentially expressed serum miRNAs in multiple sclerosis patients and to evaluate their diagnostic value in multiple sclerosis diagnosis. Studies were identified on PubMed, Google scholar and Saudi digital library up to 30 September 2019. Articles that examined miRNA expression level in MS patients compared to healthy control group were included in the review and the data were extracted by three independent author. The comprehensive Meta-Analysis version 3 software was used for meta-analysis and heterogeneity of studies was identified according to I2 value. Our literatures search identified 9 eligible articles concerning the serum miRNA as a diagnostic biomarker for multiple sclerosis in comparison to healthy control group. 19 serum miRNAs differentially expressed in MS patients were identified (8 downregulated, 11 upregulated and 1 with discordant result). In publications that provided information on specific miRNA diagnostic value, the pooled AUC was 72% (95% CI 0.65-0.78, p-value 0.00) for the overall multiple sclerosis patients and primary progressive MS (PPMS) (95% CI 0.66-0.78 p-value 0.00). A miRNA panel of four miRNAs showed high sensitivity (73%) and specificity (68%) in distinguishing multiple sclerosis from control groups. When using single miRNA (miR-145), the sensitivity increased to 79% and the specificity to 87%. The available data from the literature and this meta-analysis suggests the potential use of serum miRNA as biomarkers for early diagnosis of MS with high sensitivity and specificity in distinguishing multiple sclerosis subtypes from healthy controls.Abbreviation: MS: Multiple sclerosis; IDD: inflammatory demyelinating diseases; RRMS: relapsing-remitting Multiple sclerosis; PPMS: primary progressive Multiple sclerosis; SPMS: secondary progressive Multiple sclerosis; NMO: Neuromyelitis optica; miRNA: microRNA; ECmiRNA: extracellular microRNA; AUC: Area Under the Curve; ROC: Receiver Operator Characteristic.

Keywords: Mirna; biomarker; multiple sclerosis.