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Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.

ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs) are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS) and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA) platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS.

SUBMITTER: Keller A

PROVIDER: S-EPMC2757919 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.

Keller Andreas A Leidinger Petra P Lange Julia J Borries Anne A Schroers Hannah H Scheffler Matthias M Lenhof Hans-Peter HP Ruprecht Klemens K Meese Eckart E

PloS one 20091013 10

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs) are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cance ...[more]

PMID: 19823682

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Project description:BACKGROUND:There is a paucity of knowledge concerning erythrocytes in the aetiology of Multiple Sclerosis (MS) despite their potential to contribute to disease through impaired antioxidant capacity and altered haemorheological features. Several studies have identified an abundance of erythrocyte miRNAs and variable profiles associated with disease states, such as sickle cell disease and malaria. The aim of this study was to compare the erythrocyte miRNA profile of relapsing-remitting MS (RRMS) patients to healthy sex- and age-matched controls. METHODS:Erythrocytes were purified by density-gradient centrifugation and RNA was extracted. Following library preparation, samples were run on a HiSeq4000 Illumina instrument (paired-end 100 bp sequencing). Sequenced erythrocyte miRNA profiles (9 patients and 9 controls) were analysed by DESeq2. Differentially expressed miRNAs were validated by RT-qPCR using miR-152-3p as an endogenous control and replicated in a larger cohort (20 patients and 18 controls). After logarithmic transformation, differential expression was determined by two-tailed unpaired t-tests. Logistic regression analysis was carried out and receiver operating characteristic (ROC) curves were generated to determine biomarker potential. RESULTS:A total of 236 erythrocyte miRNAs were identified. Of twelve differentially expressed miRNAs in RRMS two showed increased expression (adj. p?<?0.05). Only modest fold-changes were evident across differentially expressed miRNAs. RT-qPCR confirmed differential expression of miR-30b-5p (0.61 fold, p?<?0.05) and miR-3200-3p (0.36 fold, p?<?0.01) in RRMS compared to healthy controls. Relative expression of miR-3200-5p (0.66 fold, NS p?=?0.096) also approached significance. MiR-3200-5p was positively correlated with cognition measured by audio-recorded cognitive screen (r?=?0.60; p?<?0.01). MiR-3200-3p showed greatest biomarker potential as a single miRNA (accuracy?=?75.5%, p?<?0.01, sensitivity?=?72.7%, specificity?=?84.0%). Combining miR-3200-3p, miR-3200-5p, and miR-30b-5p into a composite biomarker increased accuracy to 83.0% (p?<?0.05), sensitivity to 77.3%, and specificity to 88.0%. CONCLUSIONS:This is the first study to report differences in erythrocyte miRNAs in RRMS. While the role of miRNAs in erythrocytes remains to be elucidated, differential expression of erythrocyte miRNAs may be exploited as biomarkers and their potential contribution to MS pathology and cognition should be further investigated.

Dataset Information

Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.

Publications

Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.

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