Systematic analysis of brain and skull ischemic injury expression profile reveals associations of tumor immune microenvironment and cell death with ischemic stroke

Background: Previous studies showed that the stroke is a potential first sign of neoplasia. But the relationship between stroke and cancer remains unclear. Besides, ischemic stroke is a complex brain disease, which involves cell death and immunity. Thus, it is urgent to reveal the association of tumor immune microenvironment and cell death with ischemic stroke. Methods: We established a photothrombosis-induced ischemic injury model in mouse brain and skull. Then, we sequenced whole transcriptome of injured mouse brain and skull and analyzed the expression profile. To associate the stroke with cell death and cancer, we systematically performed the gene set enrichment analysis in pan-cell death (apoptosis, cuproptosis, ferroptosis, necroptosis and pyroptosis) and cancer hallmark pathways. Further, we estimated immune cell abundance after ischemic injury. Moreover, the pan-cancer genomic and prognosis analysis of ischemic-injury related gene set were performed. Results: In this study, we found that the gene expression patterns were different in temporal and spatial locations after ischemic injury. The effects on the transcriptome of the brain after skull ischemic injury was particularly large, but it could be recovered in a short period, while the effect on the skull after brain ischemic injury was long-lasting. The expression of genes related to ischemic injury is also associated with pan-cell death and cancer hallmark pathways. In addition, changes in the abundance of immune cells indicate that brain ischemic injury may disrupt its immune microenvironment for a longer time, while skull can better balance the stability of immune microenvironment. Moreover, the brain ischemic injury-related gene sets are highly correlated with a variety of tumors, especially GBM, KIRC, LGG and UVM after stroke have a greater risk of death. Conclusion: This study gives us a new understanding of the role of the skull in brain ischemic injury, and reveals the association of tumor immune microenvironment and cell death with ischemic stroke.