Immune cells are particularly important in regulating the immune and clotting systems in IS, ultimately resulting in core infarct growth, and expanding inflammatory injury to the entire ischemic territory. Molecules in immune cells particularly play vital roles in the pathogeneses. To date, many molecular features have been described to predict patient risk of suffering from IS. Nevertheless, molecular feature in peripheral blood is not specific to the origin of the biomarker. The advanced development of omics technology provides us with new opportunities to better measure the gene expression and understand the precise pathophysiological processes of IS.
The researchers noticed the vacancy of the landscape of the molecules in immune cells. To identify potential targets for effective treatment, they reviewed the studies of omics on IS, and described the gene expression profile of immune cells in peripheral blood of IS by using emerging computational tools, such as CIBERSORT and xCell. They also focused on the competing endogenous RNAs (ceRNAs), a newly proposed regulatory mechanism involving coding RNAs, non-coding RNAs, and microRNAs (miRNAs).
In addition, they further collected and combined multiple public datasets containing transcriptome expression information of peripheral blood from IS patients and healthy controls. By using standard diagnosis criteria and designed inclusion/excluded criteria for our research dataset, they identified a list of genes on basis of immune cells. Multiple computational methods are used, including CIBERSORT, Weighted Gene Co expression Network Analysis (WGCNA), Differential Expression Analysis, Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine Recursive Feature Elimination (SVM-RFE), Random Forest, etc., to analyze the characteristics of different genes related to immune cells.
Furthermore, they focused on the regulatory mechanism of molecules, by using StarBasev3.0 to construct a ceRNA network. Through the verification on human beings, animal and tool cells, they also showed the centered ceRNA pairs. By using quantitative PCR，they validated the abnormal expression of hub ceRNA pairs in their own cohort population and on basic experiments as well. Finally, the author produced a more accurate molecular signature of hub immune genes specific to their cell type and their associated ceRNA network across large publicly available datasets in the IS population.
Based on a thorough analysis of the transcriptomic molecules and single cell transcriptomics, as well as multi-dimensional experiments on ceRNA pairs, Li and Liu identified 11 distinct immune cell-related genes. The expression of HECW2 was positively correlated with lncRNAs LINC02593 and RMST through miRNAs miR-130a-3p, miR-130b-3p and miR-148b-3p in cells. ceRNA network centering around HECW2 may be a potential biomarker and promising therapeutic target for IS patients. The ceRNA network may help elucidate the mechanisms of immune cell related genes in IS and may serve as a therapeutic target.
See the article:
Profiling immune cell-related gene features and immunoregulatory ceRNA in ischemic stroke
https://doi.org/10.1186/s43556-024-00237-4
