GSE159225
RNA Sequencing and characterization of the linear and circular transcriptomes from healthy controls' and multiple sclerosis patients' leukocytes
Background and aim: The disease course and clinical phenotype in multiple sclerosis (MS) are highly variable and therefore, biomarkers are needed. Studies have shown a dysregulation in the coding and non-coding RNAs and proposed some as biomarkers. However, still none of them have reached the clinical practice. Recently, circular RNAs (circRNAs) have emerged as new players in the transcriptome that hold a great potential as biomarkers in several diseases. In this study we have performed a RNASeq profiling of patients (N=50) and healthy controls' (N=20) leukocytes in order to characterize their linear and circular transcriptomes with the final aim of finding some new potential biomarkers. Methods: Differential expression analysis was performed by DESeq and circRNA candidates were studied in a second cohort (70MS and 46HC) by RT-qPCR and in paired samples drawn during the relapse and remission phases (20 patients). Results: Among the differentially expressed circRNAs, the 96.1% is are upregulated in patients compared to controls, but similar circRNA profiles are found between MS types. The same upregulation trend was observed in females but not in males or in the linear transcriptome. The upregulation of 6 circRNAs was validated and a change in their expression was found between relapse and remission. The 6 circRNAs showed a good performance to discriminate patients from HC with a combined AUC of 0.852. Conclusion: There is global, specific and sex dependent increase of circRNA expression in MS and 6 circRNAs are proposed as potential biomarkers. Overall design: Linear and circularRNA profile from 30 MS patients' and 20 healthy controls' leukocytes