This study is aimed at identifying potential molecular mechanisms and candidate biomarkers in the left atrial regions for the diagnosis and treatment of valvular atrial fibrillation (VAF). Multibioinformatics methods, including linear models for microarray analysis (LIMMA), an SVA algorithm, CIBERSORT immune infiltration, and DNA methylation analysis, were employed. In addition, the protein-protein interaction (PPI) network, Gene Ontology (GO), and molecular pathways of differentially expressed genes (DEGs) or differential methylation regions were constructed. In all, compared with the normal rhythm group, 243 different mRNAs (29 downregulated and 214 upregulated) and 26 different lncRNAs (3 downregulated and 23 upregulated) were detected in the left atrium (LA) of atrial fibrillation (AF) patients, and the neutrophil and CD8⁺ T cell were infiltrated. Additionally, 199 different methylation sites (107 downregulated and 92 upregulated) were also identified based on DNA methylation analysis. After integration, ELOVL2, CCR2, and WEE1 were detected for differentially methylated and differentially transcribed genes. Among them, WEE1 was also a core gene identified by the competing endogenous RNA (ceRNA) network that included WEE1-KRBOX1-AS1-hsa-miR-17-5p, in VAF left atrial tissue. We combined the DNA methylation and transcriptional expression differential analysis and found that WEE1 (cg13365543) may well be a candidate gene regulated by DNA methylation modification. Moreover, KRBOX1-AS1 and WEE1 can compete endogenously and may mediate myocardial tissue infiltration into CD8⁺ T cells and participate in the AF process.

中文翻译：

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综合分析差异性免疫细胞浸润和潜在的ceRNA网络参与心房颤动的发展。

这项研究旨在确定左心房区域的潜在分子机制和候选生物标志物，以诊断和治疗瓣膜性心房颤动（VAF）。采用了多种生物信息学方法，包括用于微阵列分析的线性模型（LIMMA），SVA算法，CIBERSORT免疫浸润和DNA甲基化分析。另外，构建了蛋白质-蛋白质相互作用（PPI）网络，基因本体论（GO）以及差异表达基因（DEG）或差异甲基化区域的分子途径。总体而言，与正常节律组相比，在房颤（AF）患者的左心房（LA）中检测到243种不同的mRNA（29种下调和214种上调）和26种不同的lncRNA（3种下调和23种上调），并且中性粒细胞和CD8⁺ T细胞被浸润。另外，基于DNA甲基化分析，还鉴定出199个不同的甲基化位点（107个下调和92个上调）。整合后，检测到ELOVL2，CCR2和WEE1的差异甲基化和差异转录基因。其中，WEE1也是通过竞争性内源RNA（ceRNA）网络鉴定的核心基因，该网络包括VAF左心房组织中的WEE1-KRBOX1-AS1-hsa-miR-17-5p。我们结合了DNA甲基化和转录表达差异分析，发现WEE1（cg13365543）可能是受DNA甲基化修饰调控的候选基因。此外，KRBOX1-AS1和WEE1可以内源竞争，并且可以介导心肌组织浸润到CD8 ⁺ T细胞中并参与AF过程。