Contributions
Abstract: P1113
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Multiple Sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g. microRNAs). Indeed, some of these have been suggested as biomarkers for multiple sclerosis even though few biomarkers have reached the clinical practice.
Recently, a novel family of non-coding RNAs, circular RNAs, has emerged as a new player in the complex network of gene-expression regulation. MicroRNA regulation function through a “sponge system” and a RNA splicing regulation function have been proposed for the circular RNAs. This regulating role together with their high stability in biofluids makes them seemingly good candidates as biomarkers.
Given the dysregulation of both protein-coding and non-coding transcriptome that have been reported in multiple sclerosis patients, we hypothesised that circular RNA expression may also be altered.
Methods: Differentially expressed circRNAs were screened using an Arraystar Human circRNA Array (13617 circRNAs) in peripheral blood mononuclear cells from relapsing remitting multiple sclerosis (RR-MS) patients and healthy controls (HC). Quantitative PCR was performed in four independent cohorts including secondary progressive patients (SP-MS) and Clinically Isolated Syndrome (CIS) cases in order to validate microarray data. We further evaluated the predictive value of two of the validated circRNAs by a receiver operating characteristic (ROC) curve.
Results: We found 406 differentially expressed circRNAs (p-value< 0.05, FC>1.5) and demonstrate that after validation in a second cohort (20 untreated RR-MS patients and 18 HC), circ_0005402 (FC=0.395, p=0.0001) and circ_003452_2 (FC = 0.737, p=0.0479) are underexpressed in RR-MS patients. Those circRNAs are not significantly differentially expressed neither when comparing samples of 21 RR-MS patients at relapse and remission nor in CIS cases (10 CIS vs. 10 HC). In secondary progressive multiple sclerosis patients (17 SP-MS vs. 23 HC) circ_003452_2 is also slightly deregulated but with a trend opposite to that found for RR-MS or CIS suggesting that it could be marker of inflammation although further studies are needed.
Conclusions: We propose that both ANXA2 and circRNAs derived from ANXA2 (circ_0005402 and circ_003452_2) could be used as minimally invasive biomarkers for RR-MS.
Disclosure: LI: nothing to disclose
MMC: nothing to disclose
IP: nothing to disclose
TCT: nothing to disclose
JO: nothing to disclose
DO: nothing to disclose
This work was partially supported by the Spanish Network of Multiple Sclerosis; the Regional Council of Gipuzkoa [grant number DFG15/006] and the Department of Industry of the Basque Country [grant number ELKARTEK16/014]. LI is supported by the Department of Education of the Basque Government [grant number PRE_2016_1_0168].
Abstract: P1113
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Multiple Sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g. microRNAs). Indeed, some of these have been suggested as biomarkers for multiple sclerosis even though few biomarkers have reached the clinical practice.
Recently, a novel family of non-coding RNAs, circular RNAs, has emerged as a new player in the complex network of gene-expression regulation. MicroRNA regulation function through a “sponge system” and a RNA splicing regulation function have been proposed for the circular RNAs. This regulating role together with their high stability in biofluids makes them seemingly good candidates as biomarkers.
Given the dysregulation of both protein-coding and non-coding transcriptome that have been reported in multiple sclerosis patients, we hypothesised that circular RNA expression may also be altered.
Methods: Differentially expressed circRNAs were screened using an Arraystar Human circRNA Array (13617 circRNAs) in peripheral blood mononuclear cells from relapsing remitting multiple sclerosis (RR-MS) patients and healthy controls (HC). Quantitative PCR was performed in four independent cohorts including secondary progressive patients (SP-MS) and Clinically Isolated Syndrome (CIS) cases in order to validate microarray data. We further evaluated the predictive value of two of the validated circRNAs by a receiver operating characteristic (ROC) curve.
Results: We found 406 differentially expressed circRNAs (p-value< 0.05, FC>1.5) and demonstrate that after validation in a second cohort (20 untreated RR-MS patients and 18 HC), circ_0005402 (FC=0.395, p=0.0001) and circ_003452_2 (FC = 0.737, p=0.0479) are underexpressed in RR-MS patients. Those circRNAs are not significantly differentially expressed neither when comparing samples of 21 RR-MS patients at relapse and remission nor in CIS cases (10 CIS vs. 10 HC). In secondary progressive multiple sclerosis patients (17 SP-MS vs. 23 HC) circ_003452_2 is also slightly deregulated but with a trend opposite to that found for RR-MS or CIS suggesting that it could be marker of inflammation although further studies are needed.
Conclusions: We propose that both ANXA2 and circRNAs derived from ANXA2 (circ_0005402 and circ_003452_2) could be used as minimally invasive biomarkers for RR-MS.
Disclosure: LI: nothing to disclose
MMC: nothing to disclose
IP: nothing to disclose
TCT: nothing to disclose
JO: nothing to disclose
DO: nothing to disclose
This work was partially supported by the Spanish Network of Multiple Sclerosis; the Regional Council of Gipuzkoa [grant number DFG15/006] and the Department of Industry of the Basque Country [grant number ELKARTEK16/014]. LI is supported by the Department of Education of the Basque Government [grant number PRE_2016_1_0168].