Analysis of infiltrated immune cells in left atriums from patients with atrial fibrillation and identification of circRNA biomarkers for postoperative atrial fibrillation.
Analysis of infiltrated immune cells in left atriums from patients with atrial fibrillation and identification of circRNA biomarkers for postoperative atrial fibrillation.
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房颤患者左心房浸润免疫细胞分析及术后房颤circRNA生物标志物鉴定
DOI：
10.3389/fgene.2022.1003366
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发表时间：
2022
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
背景：房颤（AF）增加了卒中和心力衰竭的风险。术后房颤（POAF）会增加心脏手术后的死亡风险。本研究旨在探讨房颤的发病机制，分析房颤患者左心房（LA）中免疫细胞的浸润，并确定POAF的潜在环状RNA（circRNA）生物标志物。 方法：下载并处理GSE 797689、GSE 115574和GSE 97455的原始数据。采用加权基因相关网络分析法构建AF相关基因共表达网络，并对相关模块中的基因进行富集分析。应用基因集富集分析（GSEA）和基因集变异分析（GSVA）研究AF组中显著富集的通路。使用单样品GSEA分析免疫细胞的浸润。鉴定了AF患者和非AF患者之间的差异表达基因（DEG），并构建了DEG的竞争性内源性RNA（ceRNA）网络。为了筛选POAF的生物标志物，鉴定了患有或不患有POAF的患者之间的差异表达的circRNA（DECircRNA）。提取DEG的ceRNA网络中DEcircRNA和circRNA之间的交叉点，并使用支持向量机、随机森林和神经网络进一步筛选交叉点中的circRNA，以鉴定POAF的生物标志物。 结果如下：富集分析表明，这些模块中的基因在细胞外基质合成和炎症反应中富集。GSEA和GSVA结果提示AF组炎症反应相关通路明显丰富。AF患者左心房组织中巨噬细胞、肥大细胞、中性粒细胞等免疫细胞浸润明显。AF患者左心房组织中CHGB、HLA-B、LYZ、IGKV 1 -17、TYROBP等免疫基因表达明显上调，与免疫细胞浸润相关。构建DEG的ceRNA网络，发现has_circ_0006314和hsa_circ_0055387对POAF具有潜在的预测价值。 结论：细胞外基质的合成和炎症反应是AF发生发展的主要过程，AF患者与非AF患者的免疫细胞浸润存在显著差异，Has_circ_0006314和hsa_circ_0055387对POAF有潜在的预测价值。
Background: Atrial fibrillation (AF) increases the risk of stroke and heart failure. Postoperative AF (POAF) increases the risk of mortality after cardiac surgery. This study aims to explore mechanisms underlying AF, analyze infiltration of immune cells in left atrium (LA) from patients with AF, and identify potential circular RNA (circRNA) biomarkers for POAF. Methods: Raw data of GSE797689, GSE115574, and GSE97455 were downloaded and processed. AF-related gene co-expression network was constructed using weighted gene correlation network analysis and enrichment analysis of genes in relevant module was conducted. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied to investigate pathways significantly enriched in AF group. Infiltration of immune cells was analyzed using single-sample GSEA. Differentially expressed genes (DEGs) between patients with or without AF were identified and competing endogenous RNA (ceRNA) networks of DEGs were constructed. To screen biomarkers for POAF, differentially expressed circRNAs (DEcircRNAs) between patients with or without POAF were identified. Intersection between DEcircRNAs and circRNAs in ceRNA networks of DEGs were extracted and circRNAs in the intersection were further screened using support vector machine, random forest, and neural network to identify biomarkers for POAF. Results: Three modules were found to be relevant with AF and enrichment analysis indicated that genes in these modules were enriched in synthesis of extracellular matrix and inflammatory response. The results of GSEA and GSVA suggested that inflammatory response-related pathways were significantly enriched in AF group. Immune cells like macrophages, mast cells, and neutrophils were significantly infiltrated in LA tissues from patients with AF. The expression levels of immune genes such as CHGB, HLA-DRA, LYZ, IGKV1-17 and TYROBP were significantly upregulated in patients with AF, which were correlated with infiltration of immune cells. ceRNA networks of DEGs were constructed and has_circ_0006314 and hsa_circ_0055387 were found to have potential predictive values for POAF. Conclusion: Synthesis of extracellular matrix and inflammatory response were main processes involved in development and progression of AF. Infiltration of immune cells was significantly different between patients with or without AF. Has_circ_0006314 and hsa_circ_0055387 were found to have potential predictive values for POAF.
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