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FCER1G作为心源性卒中一种新的免疫相关血液生物标志物。

FCER1G as a novel immune-associated blood biomarker in cardiogenic stroke.

作者信息

Hu Yuanzheng, Li Xiangxin, Hou Kaiqi, Zhang Shoudu, Zhong Siyi, Ding Qian, Xi Wuyang, Wang Zongqing, Xing Juan, Bai Fanghui, Xu Qian

机构信息

Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal University, Nanyang, 473061, China.

Henan Provincial Key Laboratory of Stroke Prevention and Treatment, Nanyang Central Hospital, Nanyang, 473000, China.

出版信息

Heliyon. 2024 Jun 28;10(13):e33846. doi: 10.1016/j.heliyon.2024.e33846. eCollection 2024 Jul 15.

DOI:10.1016/j.heliyon.2024.e33846
PMID:39071704
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11283116/
Abstract

BACKGROUND

Cardioembolic stroke (CE) exhibits the highest recurrence rate and mortality rate among all subtypes of cerebral ischemic stroke (CIS), yet its pathogenesis remains uncertain. The immune system plays a pivotal role in the progression of CE. Growing evidence indicates that several immune-associated blood biomarkers may inform the causes of stroke. The study aimed to identify new immune-associated blood biomarkers in patients with CE and create an online predictive tool in distinguishing CE from noncardioembolic stroke (non-CE) in CIS.

METHODS

Gene expression profiles that were publicly available were obtained from the Gene Expression Omnibus (GEO). The identification of differentially expressed genes (DEGs) was conducted using the Limma package. The hub module and hub genes were identified through the application of weighted gene coexpression network analysis (WGCNA). In order to identify potential diagnostic biomarkers for CE, both the random forest (RF) model and least absolute shrinkage and selection operator (LASSO) regression analysis were employed. Concurrently, the CIBERSORT algorithm was employed to evaluate the infiltration of immune cells in CE samples and examine the correlation between the biomarkers and the infiltrating immune cells. The diagnostic gene expression in blood samples was confirmed using qRT-PCR in a self-constructed dataset. Univariate and multiple logistic regression analyses were used to identify the risk factors for CE. Subsequently, the mathematical model of the nomogram was employed via Java's "Spring Boot" framework to develop the corresponding online tool, which was then deployed on a cloud server utilizing "nginx".

RESULTS

Eleven differentially expressed genes (DEGs) that were upregulated and seven DEGs that were downregulated were identified. Through bioinformatics analysis and clinical sample verification, it was discovered that Fc Fragment of IgE Receptor Ig () could serve as a novel potential blood biomarker for CE. , along with other risk factors associated with CE, were utilized to develop a nomogram. The training and validation sets, which consisted of 65 CIS patients, yielded areas under the curve (AUCs) of 0.9722 and 0.9689, respectively. These results indicate a high level of precision in risk delineation by the nomogram. Furthermore, the associated online predictive platform has the potential to serve as a more efficacious and appropriate predictive instrument (https://www.origingenetic.com/CardiogenicStroke-FCER1G) for distinguishing between CE and non-CE.

CONCLUSION

Blood biomarker FCER1G has the potential to identify patients who are at a higher risk of cardioembolism and direct the search for occult AF.The utilization of this online tool is anticipated to yield significant implications in terms of distinguishing between CE and non-CE, as well as enhancing the optimization of treatment decision support.

摘要

背景

心源性栓塞性卒中(CE)在所有脑缺血性卒中(CIS)亚型中复发率和死亡率最高,但其发病机制仍不明确。免疫系统在CE的进展中起关键作用。越来越多的证据表明,几种与免疫相关的血液生物标志物可能有助于揭示卒中的病因。本研究旨在识别CE患者新的免疫相关血液生物标志物,并创建一个在线预测工具,以区分CIS中的CE和非心源性栓塞性卒中(非CE)。

方法

从基因表达综合数据库(GEO)获取公开可用的基因表达谱。使用Limma软件包进行差异表达基因(DEG)的鉴定。通过应用加权基因共表达网络分析(WGCNA)识别枢纽模块和枢纽基因。为了识别CE的潜在诊断生物标志物,采用了随机森林(RF)模型和最小绝对收缩和选择算子(LASSO)回归分析。同时,使用CIBERSORT算法评估CE样本中免疫细胞的浸润情况,并检查生物标志物与浸润免疫细胞之间的相关性。在自建数据集中使用qRT-PCR确认血液样本中的诊断基因表达。采用单因素和多因素逻辑回归分析确定CE的危险因素。随后,通过Java的“Spring Boot”框架使用列线图的数学模型开发相应的在线工具,然后使用“nginx”将其部署在云服务器上。

结果

鉴定出11个上调的差异表达基因(DEG)和7个下调的DEG。通过生物信息学分析和临床样本验证,发现免疫球蛋白E受体Ig的Fc片段(FcεRIγ)可作为CE一种新的潜在血液生物标志物。FcεRIγ与其他与CE相关的危险因素一起用于构建列线图。由65例CIS患者组成的训练集和验证集的曲线下面积(AUC)分别为0.9722和0.9689。这些结果表明列线图在风险划分方面具有较高的准确性。此外,相关的在线预测平台有可能成为区分CE和非CE的更有效、更合适的预测工具(https://www.origingenetic.com/CardiogenicStroke-FCER1G)。

结论

血液生物标志物FcεRIγ有可能识别心源性栓塞风险较高的患者,并指导对隐匿性房颤的筛查。预计该在线工具的使用在区分CE和非CE以及加强治疗决策支持优化方面将产生重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/f2863eb1a82a/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/51fb129e84b1/gr1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/e3e57cec0d84/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/0dcaab8bd514/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/73c15aae3175/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/0b730d85a39b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/4b76a0286f12/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/539ddc53393f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/d4a7608d9b99/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/d6f72768e82e/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/f2863eb1a82a/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/51fb129e84b1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/362854eb4be8/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/e3e57cec0d84/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/0dcaab8bd514/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/73c15aae3175/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/0b730d85a39b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/4b76a0286f12/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/539ddc53393f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/d4a7608d9b99/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/d6f72768e82e/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b776/11283116/f2863eb1a82a/mmcfigs1.jpg

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