Platelet related gene IQGAP1 contributes to the onset and abnormal immune landscape of ischemic stroke patients

Abstract

Introduction

Ischemic stroke (IS) is a complex illness resulting from a combination of numerous environmental and genetic risk factors. Recent reports have shed light on the vital role that platelets play in the pathophysiology of IS. Here, we aimed to explore the potential platelet-related genes in IS and investigate the effect of platelet-related genes in the immune microenvironment of IS.

Methods

The data of IS were retrieved from the Gene Expression Omnibus database. Firstly, we screened the platelet-related genes that were correlated with the onset of IS using differential expression analysis, enrichment analyses, and protein-protein interaction (PPI) network. Moreover, we analyzed the clinical value and functional information of platelet-related genes in IS. Finally, we explored the correlation between platelet-related genes and immune cells’ infiltration.

Results

Ten platelet-related genes that were correlated with the onset of IS were identified, among which IQGAP1 was located at the core of the PPI network. IQGAP1 was found to be expressed in the normal brain tissue and its expression was significantly elevated in IS samples. The area under the curve (AUC) values for IQGAP1 in both the GSE16561 and GSE58294 datasets were close to 1. IQGAP1 knockdown might increase OGD/R‑induced HT22 cell viability. Additionally, FoxO signaling pathway, NOD-like receptor signaling pathway, Phagosome and Platelet activation pathways were significantly activated in IS patients with high IQGAP1 expression compared to those with low IQGAP1 expression. The IS patients in the IQGAP1^high and IQGAP1^low groups showed dramatically different proportions of immune cells and immune-related functions, and the IQGAP1 expression was correlated with the immune cell’ infiltration in IS.

Conclusions

In this study, we identified the IQGAP1 might serve as a potential diagnostic marker for IS, and the IQGAP1 expression was very relevant in determining the immune cell’ infiltration in IS patients.