Integrated transcriptomics of multiple sclerosis peripheral blood mononuclear cells explored potential biomarkers for the disease

Background: Despite their importance, blood RNAs have not been comprehensively studied as potential diagnostic markers for multiple sclerosis (MS). Herein, by the integration of GSE21942 and GSE203241 microarray profiles of peripheral blood mononuclear cells, this study explored potential biomarkers for the disease. Methods: After identification of differentially expressed genes (DEGs), functional enrichment analyses were performed, and PPI and miRNA-mRNA regulatory networks were constructed. After implementing weighted gene co-expression network analysis (WGCNA) and discovering MS-specific modules, the converging results of differential expression analysis and WGCNA were subjected to machine learning methods. Lastly, the diagnostic performance of the prominent genes was evaluated by receiver operating characteristic (ROC) analysis. Results: COPG1, RPN1, and KDM3B were initially highlighted as potential biomarkers based on their acceptable diagnostic efficacy in the integrated data, as well as in both GSE141804 and GSE146383 datasets as external validation sets. However, given that they were downregulated in the integrated data while they were upregulated in the validation sets, they could not be considered as potential biomarkers for the disease. In addition to this inconsistency, evaluating their diagnostic performance in other external datasets (GSE247181, GSE59085, and GSE17393) did not reveal their diagnostic efficacy. Conclusions: This study could not unveil promising blood biomarkers for MS, possibly due to a small sample size and unaccounted confounding factors. Considering PBMCs and blood specimens as valuable sources for the identification of biomarkers, further transcriptomic analyses are needed to discover potential biomarkers for the disease.