Identification of key biomarkers associated with immune cells infiltration for myocardial injury in dermatomyositis by integrated bioinformatics analysis.
Identification of key biomarkers associated with immune cells infiltration for myocardial injury in dermatomyositis by integrated bioinformatics analysis.
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DOI：
10.1186/s13075-023-03052-4
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发表时间：
2023-04-28
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
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作者：
皮肌炎 (DM) 是一种获得性自身免疫性疾病，可对包括心肌在内的多种器官造成损害。然而，糖尿病心肌损伤的机制尚未完全清楚。在这项研究中，我们利用基因表达综合 (GEO) 数据库中公开的数据集来识别在 DM 和心肌炎的免疫系统过程中丰富的中枢基因。采用加权基因共表达网络分析（WGCNA）、差异表达基因（DEG）分析、蛋白质-蛋白质相互作用（PPI）和基因本体（GO）分析来识别这些中心基因。然后我们使用 CIBERSORT 方法分别分析了 DM 骨骼肌标本和心肌炎心肌标本中的免疫细胞浸润情况。进行相关分析以研究关键基因与浸润免疫细胞之间的关系。最后，我们通过 miRNet 预测了 hub-gene 的调控 miRNA，并验证了它们在在线数据集和临床样本中的表达。通过综合生物信息学分析，我们在糖尿病和心肌炎数据库中分别鉴定了 10 个和 5 个在免疫系统过程中富集的中心基因。随后 hub 基因之间的交叉点是 IFIT3、OAS3、ISG15 和 RSAD2。我们发现，与健康对照相比，DM 和心肌炎中的 M2 巨噬细胞增多，与 DM 和心肌炎中 IFIT3、OAS3、ISG15 和 RSAD2 的表达呈正相关。基因功能富集分析（GSEA）显示，IFIT3、OAS3、ISG15和RSAD2主要富集于I型干扰素（IFN）信号通路、细胞对I型干扰素的反应以及对I型干扰素的反应。最后，我们验证了miR-146a-5p的表达在有心肌损伤的DM中显着高于没有心肌损伤的DM（p = 0.0009）。我们的研究结果表明，IFIT3、OAS3、ISG15 和 RSAD2 可能在 DM 心肌损伤的潜在机制中发挥关键作用。血清 miR-146a-5p 可能是糖尿病心肌损伤的潜在生物标志物。
Dermatomyositis (DM) is an acquired autoimmune disease that can cause damage to various organs, including the heart muscle. However, the mechanisms underlying myocardial injury in DM are not yet fully understood. In this study, we utilized publicly available datasets from the Gene Expression Omnibus (GEO) database to identify hub-genes that are enriched in the immune system process in DM and myocarditis. Weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs) analysis, protein–protein interaction (PPI), and gene ontology (GO) analysis were employed to identify these hub-genes. We then used the CIBERSORT method to analyze immune cell infiltration in skeletal muscle specimens of DM and myocardium specimens of myocarditis respectively. Correlation analysis was performed to investigate the relationship between key genes and infiltrating immune cells. Finally, we predicted regulatory miRNAs of hub-genes through miRNet and validated their expression in online datasets and clinical samples. Using integrated bioinformatics analysis, we identified 10 and 5 hub-genes that were enriched in the immune system process in the database of DM and myocarditis respectively. The subsequent intersections between hub-genes were IFIT3, OAS3, ISG15, and RSAD2. We found M2 macrophages increased in DM and myocarditis compared to the healthy control, associating with the expression of IFIT3, OAS3, ISG15, and RSAD2 in DM and myocarditis positively. Gene function enrichment analysis (GSEA) showed that IFIT3, OAS3, ISG15, and RSAD2 were mainly enriched in type I interferon (IFN) signaling pathway, cellular response to type I interferon, and response to type I interferon. Finally, we verified that the expression of miR-146a-5p was significantly higher in the DM with myocardial injury than those without myocardial injury (p = 0.0009). Our findings suggest that IFIT3, OAS3, ISG15, and RSAD2 may play crucial roles in the underlying mechanism of myocardial injury in DM. Serum miR-146a-5p could be a potential biomarker for myocardial injury in DM.
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影响因子：
16.6
作者：
Buang N;Tapeng L;Gray V;Sardini A;Whilding C;Lightstone L;Cairns TD;Pickering MC;Behmoaras J;Ling GS;Botto M
通讯作者：
Botto M
影响因子：
7.3
作者：
Jiang, Tingwang;Huang, Yuanlan;Gao, Mingzhu
通讯作者：
Gao, Mingzhu
影响因子：
13.3
作者：
Casey, Kerry A.;Smith, Michael A.;White, Wendy, I
通讯作者：
White, Wendy, I
DOI：
10.1186/s12968-016-0308-4
发表时间：
2016-11-30
期刊：
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
影响因子：
--
作者：
Haaf P;Garg P;Messroghli DR;Broadbent DA;Greenwood JP;Plein S
通讯作者：
Plein S
影响因子：
4.7
作者：
Diederichsen, L. P.;Simonsen, J. A.;Jacobsen, S.
通讯作者：
Jacobsen, S.