PDF(Pubmed)
Abstract：
UNASSIGNED: Type 2 diabetes mellitus (T2DM) is a major cause of atherosclerosis (AS). However, definitive evidence regarding the common molecular mechanisms underlying these two diseases are lacking. This study aimed to investigate the mechanisms underlying the association between T2DM and AS.
UNASSIGNED: The gene expression profiles of T2DM (GSE159984) and AS (GSE100927) were obtained from the Gene Expression Omnibus, after which overlapping differentially expressed gene identification, bioinformatics enrichment analyses, protein-protein interaction network construction, and core genes identification were performed. We confirmed the discriminatory capacity of core genes using receiver operating curve analysis. We further identified transcription factors using TRRUST database to build a transcription factor-mRNA regulatory network. Finally, the immune infiltration and the correlation between core genes and differential infiltrating immune cells were analyzed.
UNASSIGNED: A total of 27 overlapping differentially expressed genes were identified under the two-stress conditions. Functional analyses revealed that immune responses and transcriptional regulation may be involved in the potential pathogenesis. After protein-protein interaction network deconstruction, external datasets, and qRT-PCR experimental validation, four core genes (IL1B, C1QA, CCR5, and MSR1) were identified. ROC analysis further showed the reliable value of these core genes. Four common differential infiltrating immune cells (B cells, CD4+ T cells, regulatory T cells, and M2 macrophages) between T2DM and AS datasets were selected based on immune cell infiltration. A significant correlation between core genes and common differential immune cells. Additionally, five transcription factors (RELA, NFκB1, JUN, YY1, and SPI1) regulating the transcription of core genes were mined using upstream gene regulator analysis.
UNASSIGNED: In this study, common target genes and co-immune infiltration landscapes were identified between T2DM and AS. The relationship among five transcription factors, four core genes, and four immune cells profiles may be crucial to understanding T2DM complicated with AS pathogenesis and therapeutic direction.
UNASSIGNED: The gene expression profiles of T2DM (GSE159984) and AS (GSE100927) were obtained from the Gene Expression Omnibus, after which overlapping differentially expressed gene identification, bioinformatics enrichment analyses, protein-protein interaction network construction, and core genes identification were performed. We confirmed the discriminatory capacity of core genes using receiver operating curve analysis. We further identified transcription factors using TRRUST database to build a transcription factor-mRNA regulatory network. Finally, the immune infiltration and the correlation between core genes and differential infiltrating immune cells were analyzed.
UNASSIGNED: A total of 27 overlapping differentially expressed genes were identified under the two-stress conditions. Functional analyses revealed that immune responses and transcriptional regulation may be involved in the potential pathogenesis. After protein-protein interaction network deconstruction, external datasets, and qRT-PCR experimental validation, four core genes (IL1B, C1QA, CCR5, and MSR1) were identified. ROC analysis further showed the reliable value of these core genes. Four common differential infiltrating immune cells (B cells, CD4+ T cells, regulatory T cells, and M2 macrophages) between T2DM and AS datasets were selected based on immune cell infiltration. A significant correlation between core genes and common differential immune cells. Additionally, five transcription factors (RELA, NFκB1, JUN, YY1, and SPI1) regulating the transcription of core genes were mined using upstream gene regulator analysis.
UNASSIGNED: In this study, common target genes and co-immune infiltration landscapes were identified between T2DM and AS. The relationship among five transcription factors, four core genes, and four immune cells profiles may be crucial to understanding T2DM complicated with AS pathogenesis and therapeutic direction.
摘要：
■2型糖尿病（T2DM）是动脉粥样硬化（AS）的主要原因。然而,缺乏关于这两种疾病的共同分子机制的明确证据。本研究旨在探讨T2DM与AS之间关联的潜在机制。
■T2DM（GSE159984）和AS（GSE100927）的基因表达谱从基因表达综述获得，之后，重叠差异表达的基因鉴定，生物信息学富集分析，蛋白质-蛋白质相互作用网络的构建，并进行核心基因鉴定。我们使用受试者工作曲线分析证实了核心基因的判别能力。我们使用TRRUST数据库进一步鉴定了转录因子，以建立转录因子-mRNA调控网络。最后,分析了免疫浸润情况以及核心基因与差异浸润免疫细胞之间的相关性。
■在双胁迫条件下鉴定出总共27个重叠的差异表达基因。功能分析表明，免疫反应和转录调控可能参与潜在的发病机制。蛋白质-蛋白质相互作用网络解构后，外部数据集，和qRT-PCR实验验证，四个核心基因(IL1B，C1QA,CCR5和MSR1)被鉴定。ROC分析进一步显示了这些核心基因的可靠价值。四种常见的差异浸润性免疫细胞(B细胞，CD4+T细胞,调节性T细胞,基于免疫细胞浸润选择T2DM和AS数据集之间的M2巨噬细胞）。核心基因与普通差异免疫细胞之间存在显著相关性。此外,五个转录因子(RELA，NFκB1,JUN,YY1和SPI1）调节核心基因的转录使用上游基因调节因子分析来挖掘。
■在这项研究中，确定了T2DM和AS之间的共同靶基因和共同免疫浸润景观。五个转录因子之间的关系，四个核心基因，4种免疫细胞谱可能对理解T2DM并发AS的发病机制和治疗方向至关重要。
■T2DM（GSE159984）和AS（GSE100927）的基因表达谱从基因表达综述获得，之后，重叠差异表达的基因鉴定，生物信息学富集分析，蛋白质-蛋白质相互作用网络的构建，并进行核心基因鉴定。我们使用受试者工作曲线分析证实了核心基因的判别能力。我们使用TRRUST数据库进一步鉴定了转录因子，以建立转录因子-mRNA调控网络。最后,分析了免疫浸润情况以及核心基因与差异浸润免疫细胞之间的相关性。
■在双胁迫条件下鉴定出总共27个重叠的差异表达基因。功能分析表明，免疫反应和转录调控可能参与潜在的发病机制。蛋白质-蛋白质相互作用网络解构后，外部数据集，和qRT-PCR实验验证，四个核心基因(IL1B，C1QA,CCR5和MSR1)被鉴定。ROC分析进一步显示了这些核心基因的可靠价值。四种常见的差异浸润性免疫细胞(B细胞，CD4+T细胞,调节性T细胞,基于免疫细胞浸润选择T2DM和AS数据集之间的M2巨噬细胞）。核心基因与普通差异免疫细胞之间存在显著相关性。此外,五个转录因子(RELA，NFκB1,JUN,YY1和SPI1）调节核心基因的转录使用上游基因调节因子分析来挖掘。
■在这项研究中，确定了T2DM和AS之间的共同靶基因和共同免疫浸润景观。五个转录因子之间的关系，四个核心基因，4种免疫细胞谱可能对理解T2DM并发AS的发病机制和治疗方向至关重要。
