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1 型糖尿病患者外周血单个核细胞的转录组分析。

Transcriptome analysis of peripheral blood mononuclear cells in patients with type 1 diabetes mellitus.

机构信息

Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China.

Department of Endocrinology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, Jiangsu, 215300, China.

出版信息

Endocrine. 2022 Nov;78(2):270-279. doi: 10.1007/s12020-022-03163-z. Epub 2022 Aug 17.

Abstract

PURPOSE

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic β cells. The goal of this study was to explore potential biological biomarkers for T1DM.

METHODS

Two microarray datasets (GSE55098 and GSE156035) about human peripheral blood mononuclear cells (PBMCs) were systematically extracted from the Gene Expression Omnibus (GEO) database. Common genes were identified from the perspective of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) respectively, and hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis. We also observed the expression of these hub genes in some common autoimmune diseases and predicted transcription factors (TFs) that might be associated with these genes.

RESULTS

Seven hub genes (DDIT4, ESCO2, SH3BP4, PRICKLE1, EPM2AIP1, KCNJ15 and GRM8) were finally identified. Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of T1DM. Gene set enrichment analysis (GSEA) suggested that most of these hub genes may be mainly involved in the changes of biological functions such as inflammation, infection, immunity, cancer, and apoptosis. Further, compared with the control group, the expression levels of these hub genes also changed in some other autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary biliary cholangitis (PBC), etc., indicating that they might be the common targets of these autoimmune diseases.

CONCLUSIONS

The present study identified novel genes associated with T1DM from the PBMCs perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of T1DM.

摘要

目的

1 型糖尿病(T1DM)是一种慢性自身免疫性疾病,其特征是胰腺β细胞的破坏。本研究旨在探索 T1DM 的潜在生物学生物标志物。

方法

从基因表达综合数据库(GEO)中系统地提取了两个关于人外周血单个核细胞(PBMC)的微阵列数据集(GSE55098 和 GSE156035)。分别从差异表达基因(DEGs)和加权基因共表达网络分析(WGCNA)的角度确定共同基因,并通过最小绝对收缩和选择算子(LASSO)分析确定枢纽基因。我们还观察了这些枢纽基因在一些常见自身免疫性疾病中的表达,并预测了可能与这些基因相关的转录因子(TFs)。

结果

最终确定了 7 个枢纽基因(DDIT4、ESCO2、SH3BP4、PRICKLE1、EPM2AIP1、KCNJ15 和 GRM8)。受试者工作特征(ROC)分析表明,这些基因的高表达可以很好地预测 T1DM 的发生。基因集富集分析(GSEA)表明,这些枢纽基因中的大多数可能主要参与炎症、感染、免疫、癌症和细胞凋亡等生物学功能的变化。此外,与对照组相比,这些枢纽基因的表达水平在其他一些自身免疫性疾病中也发生了变化,如类风湿关节炎(RA)、系统性红斑狼疮(SLE)、原发性胆汁性胆管炎(PBC)等,表明它们可能是这些自身免疫性疾病的共同靶点。

结论

本研究从 PBMC 角度鉴定了与 T1DM 相关的新基因,这可能为 T1DM 的早期诊断、监测、评估和预测提供新的思路。

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