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基于冠状动脉疾病患者脂肪组织基因表达谱的亚组鉴定。

Subgroup Identification with Gene Expression Profiles of Adipose Tissue in Patients with Coronary Artery Disease.

机构信息

Department of Cardiology, The Xuzhou School of Clinical Medicine of Nanjing Medical University; Xuzhou Central Hospital.

Department of Ultrasound, The Third Affiliated Hospital of Xuzhou Medical University.

出版信息

Int Heart J. 2021 Nov 30;62(6):1199-1206. doi: 10.1536/ihj.21-189. Epub 2021 Nov 6.

Abstract

Among many diseases, coronary artery disease (CAD) is the primary cause of mortality and morbidity worldwide. With the aim of revealing the underlying genetic characteristics of the CAD subtypes, we recruited patients with CAD and categorized them into subgroups according to the transcriptome expression profiles of the adipose tissue.With the removal of the batch effect, consensus clustering was employed to determine the subgroup numbers. Subgroup-specific genes were determined to conduct analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Weighted gene co-expression network analysis (WGCNA) revealed the subgroup-specific WGCNA modules. Moreover, gene set enrichment analysis (GSEA) was conducted. Overrepresentation enrichment analysis (OEA) of subgroup-specific signatures was also conducted to reveal the significant gene module associated with the corresponding clinical characteristics.After the removal of the batch effect, 77 CAD objects were divided into three subgroups. It was observed that the patients in subgroup III tended to be fat. After analyzing the dominant pathways of each subgroup, we discovered that the protein digestion and absorption pathway was specifically upregulated in subgroup I, which might result from the lowest proportion of the epicardial adipose tissue (EAT) sample. Moreover, subgroup II patients had genetic characteristics of high expression of complement and coagulation cascades and TNF signaling pathway. Furthermore, Th17 cell differentiation was significantly upregulated in subgroup III, indicating that Th17 cell differentiation is related to the clinical characteristics of body mass index (BMI).In conclusion, the genetic classification of CAD subjects indicated that subjects from different subgroups may exhibit specific gene expression patterns, suggesting that more personalized treatment should be applied to patients in each subgroup.

摘要

在众多疾病中,冠心病(CAD)是全球死亡和发病的主要原因。为了揭示 CAD 亚型的潜在遗传特征,我们招募了 CAD 患者,并根据脂肪组织的转录组表达谱将他们分为亚组。在去除批次效应后,采用共识聚类确定亚组数量。确定亚组特异性基因,进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析。加权基因共表达网络分析(WGCNA)揭示了亚组特异性 WGCNA 模块。此外,还进行了基因集富集分析(GSEA)。对亚组特异性特征进行了过度表达富集分析(OEA),以揭示与相应临床特征相关的显著基因模块。去除批次效应后,77 个 CAD 对象分为 3 个亚组。观察到亚组 III 的患者倾向于肥胖。分析每个亚组的主要途径后,我们发现蛋白消化吸收途径在亚组 I 中特异性上调,这可能是由于心外膜脂肪组织(EAT)样本比例最低所致。此外,亚组 II 患者的补体和凝血级联及 TNF 信号通路的高表达具有遗传特征。此外,亚组 III 中 Th17 细胞分化明显上调,表明 Th17 细胞分化与体重指数(BMI)的临床特征有关。综上所述,CAD 受试者的遗传分类表明,来自不同亚组的受试者可能表现出特定的基因表达模式,这表明应该为每个亚组的患者提供更个性化的治疗。

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