Exploring of mechanisms and predicting of potential drugs of the comorbidity between migraine and multiple sclerosis based on bioinformatics analysis of transcriptome data

Abstract Background: Migraine and multiple sclerosis (MS) are frequent clinical partners, but the mechanisms and treatments of the comorbidity of the two are still unclear. This study aimed to investigate the shared mechanisms and predict potential drugs of migraine and MS with a view to provide new clues and approaches for clinical management. Methods: So firstly, PRJEB40032 (migraine) from ENA and GSE21942 (MS) from GEO were analyzed for differentially expressed genes (DEGs). And then, gene clusters and hub genes for common DEGs were identified, as well as functional annotation and pathway enrichment analysis were performed for exploring the gene signatures and molecular mechanisms of the comorbidity. Further, hub genes and critical pathways were evaluated by the receiver operating characteristic curves (ROC) and previous studies. Finally, the drugs targeting hub genes and critical pathways were predicted, of which drugs targeting both hub genes and critical pathways were further screened. Results: 112 DEGs were identified to be related to the comorbidity of migraine and MS, of which 9 hub genes ( IL1B , JUN , CXCL8 , FOS , ICAM1 , MMP9 , EGR1 , LCN2 , MMP8 ) were of high diagnostic value for the comorbidity. Functional annotation and pathway enrichment analysis showed that inflammatory response regulation and reactive oxygen species metabolism played a major role, and multiple pathways such as IL17 signaling pathway were involved in the comorbidity. 5 hub genes and 17 critical pathways were further evaluated, with predicted 112 and 535 drugs, respectively, including aspirin (non-steroidal anti-inflammatory drugs (NSAIDs)), baclofen (gamma-aminobutyric acid (GABA) receptor agonist), and melatonin (antioxidant). Ultimately, 10 drugs targeting both hub genes and critical pathways were screened, mainly anti-inflammatory drugs, immunological agents and antineoplastic drugs, in which there were three IL-1β inhibitors with high potential research value for the treatments of the comorbidity. Conclusions: We found that inflammation and oxidative stress were closely related to the comorbidity of migraine and multiple sclerosis. We also predicted some drugs for drawing on from each other and the comorbidity, such as NSAIDs, GABA receptor agonists/analogs andIL-1β inhibitors.