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
• multiple sclerosis
• biomarker

Acknowledgements

We thank Ms. Sarah L Cupler and Mr. Turki Sobahy for critical reading of the manuscript and providing constructive comments.

Competing interests

The authors declare that they have no competing interests.

Availability of data and material

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Authors’ contributions

SAZ designed the study, data extraction and drafted the manuscript for intellectual content and undertook acquisition of data and interpretation of results. JJS revised the extracted data, created the tables and drafted the manuscript for intellectual content. RA Assisted in statistical analysis, acquisition and interpretation of data and results. ASA and DMA conducted data extraction. EJC revised and edited the study.

Additional information

Funding

No relevant funding or disclosures to be made.