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

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.

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".

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 (FCER1G) could serve as a novel potential blood biomarker for CE. FCER1G, 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.

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.