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Abstract：
BACKGROUND: Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS) are complex disorders with unclear origins, underscoring the need for in-depth molecular investigations into their mechanisms. The main aim of this study is to identify the shared key genes between LQTS and BWS, shedding light on potential common molecular pathways underlying these syndromes.
METHODS: The LQTS and BWS datasets are available for download from the GEO database. Differential expression genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was used to detect significant modules and central genes. Gene enrichment analysis was performed. CIBERSORT was used for immune cell infiltration analysis. The predictive protein interaction (PPI) network of core genes was constructed using STRING, and miRNAs regulating central genes were screened using TargetScan.
RESULTS: Five hundred DEGs associated with Long QT Syndrome and Beckwith-Wiedemann Syndrome were identified. GSEA analysis revealed enrichment in pathways such as T cell receptor signaling, MAPK signaling, and adrenergic signaling in cardiac myocytes. Immune cell infiltration indicated higher levels of memory B cells and naive CD4 T cells. Four core genes (CD8A, ICOS, CTLA4, LCK) were identified, with CD8A and ICOS showing low expression in the syndromes and high expression in normal samples, suggesting potential inverse regulatory roles.
CONCLUSIONS: The expression of CD8A and ICOS is low in long QT syndrome and Beckwith-Wiedemann syndrome, indicating their potential as key genes in the pathogenesis of these syndromes. The identification of shared key genes between LQTS and BWS provides insights into common molecular mechanisms underlying these disorders, potentially facilitating the development of targeted therapeutic strategies.
METHODS: The LQTS and BWS datasets are available for download from the GEO database. Differential expression genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was used to detect significant modules and central genes. Gene enrichment analysis was performed. CIBERSORT was used for immune cell infiltration analysis. The predictive protein interaction (PPI) network of core genes was constructed using STRING, and miRNAs regulating central genes were screened using TargetScan.
RESULTS: Five hundred DEGs associated with Long QT Syndrome and Beckwith-Wiedemann Syndrome were identified. GSEA analysis revealed enrichment in pathways such as T cell receptor signaling, MAPK signaling, and adrenergic signaling in cardiac myocytes. Immune cell infiltration indicated higher levels of memory B cells and naive CD4 T cells. Four core genes (CD8A, ICOS, CTLA4, LCK) were identified, with CD8A and ICOS showing low expression in the syndromes and high expression in normal samples, suggesting potential inverse regulatory roles.
CONCLUSIONS: The expression of CD8A and ICOS is low in long QT syndrome and Beckwith-Wiedemann syndrome, indicating their potential as key genes in the pathogenesis of these syndromes. The identification of shared key genes between LQTS and BWS provides insights into common molecular mechanisms underlying these disorders, potentially facilitating the development of targeted therapeutic strategies.
摘要：
背景：长QT综合征（LQTS）和Beckwith-Wiedemann综合征（BWS）是起源不明的复杂疾病，强调需要对其机制进行深入的分子研究。这项研究的主要目的是确定LQTS和BWS之间的共享关键基因，揭示这些综合征潜在的共同分子途径。
方法：LQTS和BWS数据集可从GEO数据库下载。鉴定了差异表达基因(DEGs)。加权基因共表达网络分析(WGCNA)用于检测重要模块和中心基因。进行基因富集分析。CIBERSORT用于免疫细胞浸润分析。使用STRING构建核心基因的预测性蛋白质相互作用（PPI）网络，使用TargetScan筛选调节中心基因的miRNA。
结果：确定了与长QT综合征和Beckwith-Wiedemann综合征相关的500个DEG。GSEA分析揭示了T细胞受体信号通路的富集，MAPK信号，和心肌细胞中的肾上腺素能信号。免疫细胞浸润表明较高水平的记忆B细胞和幼稚CD4T细胞。四个核心基因（CD8A，ICOS,CTLA4，LCK）被识别，CD8A和ICOS在证候中低表达，在正常样本中高表达，提示潜在的反向调节作用。
结论：长QT综合征和Beckwith-Wiedemann综合征中CD8A和ICOS的表达低，表明它们可能是这些综合征发病机制中的关键基因。LQTS和BWS之间共享关键基因的鉴定提供了对这些疾病的共同分子机制的见解。有可能促进有针对性的治疗策略的发展。
方法：LQTS和BWS数据集可从GEO数据库下载。鉴定了差异表达基因(DEGs)。加权基因共表达网络分析(WGCNA)用于检测重要模块和中心基因。进行基因富集分析。CIBERSORT用于免疫细胞浸润分析。使用STRING构建核心基因的预测性蛋白质相互作用（PPI）网络，使用TargetScan筛选调节中心基因的miRNA。
结果：确定了与长QT综合征和Beckwith-Wiedemann综合征相关的500个DEG。GSEA分析揭示了T细胞受体信号通路的富集，MAPK信号，和心肌细胞中的肾上腺素能信号。免疫细胞浸润表明较高水平的记忆B细胞和幼稚CD4T细胞。四个核心基因（CD8A，ICOS,CTLA4，LCK）被识别，CD8A和ICOS在证候中低表达，在正常样本中高表达，提示潜在的反向调节作用。
结论：长QT综合征和Beckwith-Wiedemann综合征中CD8A和ICOS的表达低，表明它们可能是这些综合征发病机制中的关键基因。LQTS和BWS之间共享关键基因的鉴定提供了对这些疾病的共同分子机制的见解。有可能促进有针对性的治疗策略的发展。
