Blue module candidate hub genes.

The fluctuating weakness in myasthenia gravis (MG) is clinically described as the “morning improvement and evening worsening” pattern; MG is commonly associated with sleep disorders. However, there remains a paucity of research investigating the relationship between MG and circadian rhythms. This study seeks to identify pivotal circadian rhythm genes (CRGs) and characterize immune cell infiltration in MG, while exploring their potential roles in MG pathogenesis. MG data were obtained from the Gene Expression Omnibus (GEO) database. Initially, differentially expressed circadian rhythm genes between MG and control samples were identified through differential expression analysis. Subsequently, to elucidate the functional roles of differentially expressed CRGs, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression were applied to identify the hub CRGs. The diagnostic utility of hub genes was evaluated using the receiver operating characteristic curve, and their protein expression levels in the serum of patients with MG were assessed utilizing enzyme-linked immunosorbent assay. Additionally, we examined the extent of immune cell infiltration in MG and explored its relationship with the identified hub genes. We analyzed the immune infiltration profile in MG and their correlation with the identified hub genes. The GO enrichment analysis revealed significant enrichment of differentially expressed genes in circadian rhythm-related biological processes. Our investigation identified two hub CRGs that exhibit high diagnostic specificity and sensitivity and are significantly upregulated in serum samples from MG patients. Furthermore, Immune cells were correlated with hub genes. Our findings suggest a potential circadian rhythm disorder in MG, which may offer novel biomarkers and therapeutic strategies for future research.重症肌无力（myasthenia gravis, MG）的波动性肌无力在临床上被描述为“晨轻暮重”模式；MG常伴随睡眠障碍。然而目前针对MG与昼夜节律之间关联的研究仍较为匮乏。本研究旨在鉴定关键昼夜节律基因（circadian rhythm genes, CRGs），并表征MG中的免疫细胞浸润情况，同时探究它们在MG发病机制中的潜在作用。MG数据集源自基因表达综合数据库（Gene Expression Omnibus, GEO）。首先通过差异表达分析，鉴定出MG样本与对照样本之间的差异表达昼夜节律基因。随后，为阐明差异表达CRGs的功能机制，我们开展了基因本体论（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路富集分析。最后，采用加权基因共表达网络分析（weighted gene co-expression network analysis, WGCNA）以及最小绝对收缩和选择算子（least absolute shrinkage and selection operator, LASSO）回归模型，以筛选核心CRGs。使用受试者工作特征曲线（receiver operating characteristic curve）评估核心基因的诊断效能，并通过酶联免疫吸附试验（enzyme-linked immunosorbent assay）检测MG患者血清中核心基因的蛋白质表达水平。此外，我们分析了MG样本中的免疫细胞浸润程度，并探究其与鉴定出的核心基因之间的关联。GO富集分析结果显示，差异表达基因在昼夜节律相关的生物学过程中显著富集。本研究共鉴定出两个核心CRGs，二者在MG患者血清样本中显著上调，且具备较高的诊断特异性与敏感性。进一步分析发现，免疫细胞浸润水平与核心基因存在显著相关性。本研究结果表明MG可能存在潜在的昼夜节律紊乱，该发现可为未来的MG研究提供全新的生物标志物与治疗策略。