Methylation factors as biomarkers of fibromyalgia.

Background: Fibromyalgia (FM) is a common and intractable chronic musculoskeletal pain syndrome, but its exact underlying mechanisms are unknown. This study sought to identify biomarkers of FM and the underlying molecular mechanisms of the disease. Methods: FM-related gene expression profiles (GSE67311) and methylation profiles (GSE85506) were obtained from the Gene Expression Omnibus database, and a differential expression analysis was performed to identify the methylation factors. Subsequently, an enrichment analysis and gene set enrichment analysis (GSEA) were conducted to examine the methylation factors. In addition, the transcriptional regulators of the methylation factors were predicted, and key methylation factors were identified by a receiver operating characteristic curve analysis and nomogram models. Finally, the relationship between FM and cell death (pyroptosis, necroptosis, and cuproptosis) was assessed by a GSEA and gene set variation analysis. Results: A total of 455 methylation factors were identified. The enrichment analysis and GSEA results showed that methylation factors were clearly involved in the biological functions and signaling pathways related to neural, immune inflammation, and pain responses. The transcriptional regulator specificity protein 1 (SP1) may have a broad regulatory role. Finally, seven key methylation factors were identified, of which amino beta (A4) precursor protein binding family B member 2 (APBB2), A-kinase anchor protein 12 (AKAP12), and cluster of differentiation 38 (CD38) had strong clinical diagnostic power. In addition, AKAP12 and CD38 were significantly and negatively associated with sepsis, necrotizing sepsis, and cupular sepsis. Conclusions: Our study suggests that FM is associated with deoxyribonucleic acid methylation. The methylation factors APBB2, AKAP12, and CD38 may be potential biomarkers and should be further examined to provide a new biological framework of the possible disease mechanisms underlying FM.