Huang Chengyu, Zhang Nan, Wei Mengxin, Pan Qinchun, Cheng Chunyan, Lu Ke-Er, Mo Jianwen, Chen Yixuan
Department of Basic Science, Yuandong International Academy of Life Sciences, Hong Kong, China.
Biology Institute, Guangxi Academy of Sciences, Nanning, China.
Ann Transl Med. 2023 Feb 28;11(4):169. doi: 10.21037/atm-22-6631. Epub 2023 Feb 21.
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.
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.
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.
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.
纤维肌痛（FM）是一种常见且难治的慢性肌肉骨骼疼痛综合征，但其确切的潜在机制尚不清楚。本研究旨在确定FM的生物标志物以及该疾病的潜在分子机制。
从基因表达综合数据库中获取FM相关的基因表达谱（GSE67311）和甲基化谱（GSE85506），并进行差异表达分析以鉴定甲基化因子。随后，进行富集分析和基因集富集分析（GSEA）以研究甲基化因子。此外，预测甲基化因子的转录调节因子，并通过受试者工作特征曲线分析和列线图模型鉴定关键甲基化因子。最后，通过GSEA和基因集变异分析评估FM与细胞死亡（焦亡、坏死性凋亡和铜死亡）之间的关系。
共鉴定出455个甲基化因子。富集分析和GSEA结果表明，甲基化因子明显参与了与神经、免疫炎症和疼痛反应相关的生物学功能和信号通路。转录调节因子特异性蛋白1（SP1）可能具有广泛的调节作用。最后，鉴定出7个关键甲基化因子，其中氨基β（A4）前体蛋白结合家族B成员2（APBB2）、A激酶锚定蛋白12（AKAP12）和分化簇38（CD38）具有较强的临床诊断能力。此外，AKAP12和CD38与脓毒症、坏死性脓毒症和杯状脓毒症显著负相关。
我们的研究表明FM与脱氧核糖核酸甲基化有关。甲基化因子APBB2、AKAP12和CD38可能是潜在的生物标志物，应进一步研究以提供FM潜在疾病机制的新生物学框架。
