A Study of Long Noncoding RNAs Expression Levels in the CSF of Multiple Sclerosis Patients

Objective: Our aim is to study the cerebrospinal fluid (CSF) expression profiles of long noncoding RNAs (lncRNAs) to identify molecular signatures of primary progressive multiple sclerosis (PPMS) and relapsing remitting multiple sclerosis (RRMS).

Background: Regulatory lncRNAs have been functionally implicated in many neurodegenerative disorders. Also, their expression profiles have been of diagnostic and prognostic value in several diseases. Multiple sclerosis (MS) is an inflammatory neurodegenerative disease. There is no single clinical test for the diagnosis of PPMS and RRMS, the two main clinical manifestations of MS. Our goal was to identify molecular markers for PPMS and RRMS in the CSF of patients with MS.

Design/Methods: Total RNA was purified from CSF samples from treatment-naive patients with PPMS (n=4) , RRMS (n=4), and healthy donors (n=4). Differential strand-specific RNA sequencing analysis of lncRNAs was completed of the 12 CSF samples. Statistically significant lncRNAs were determined by Volcano plot analysis by identifying all genes of adjusted p-values of less than 0.1 and a log2fold change greater than 1. Gene ontology, splice variant expression, and SNP/INDEL analyses were performed on the statistically significant lncRNAs.

Results: The RNA sequencing analysis of CSF samples identified 75 lncRNAs that were differentially expressed in PPMS patients in comparison to RRMS patients of which only 7 lncRNAs expression levels were statistically significant.

Conclusions: A differential RNA sequencing analysis of CSF samples from PPMS and RRMS patients identified 7 lncRNAs with significantly different expression levels. These lncRNAs expression profiles could potentially serve as molecular markers for the diagnosis and prognosis of PPMS and RRMS. Further investigations will elucidate the functional meaning of their unique expression levels in PPMS and RRMS.