AUTHOR=Zhang Chao , Wang Lisi , Guo Yunmiao , Feng Wei 

TITLE=Systematic analysis of brain and skull ischemic injury expression profiles reveals associations of the tumor immune microenvironment and cell death with ischemic stroke

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1082546

DOI=10.3389/fimmu.2022.1082546

ISSN=1664-3224

ABSTRACT=Background: Previous studies showed that the stroke is a potential first sign of neoplasia, but the relationship between stroke and cancer remains unclear. As a complex brain disease, ischemic stroke involves cell death and immunity. Thus, it is necessary to investigate 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, respectively. Then, we sequenced the whole transcriptome of injured mouse brain and skull, and analyzed the expression profiles. To investigate the association of 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, the time-dependent immune cell abundance variations after ischemic injury were estimated. And the pan-cancer genomic and prognosis analysis of ischemic injury-related gene set were also performed.
Results: In this study, we found there exist temporal and spatial differences in the gene expression patterns for both brain and skull with ischemic injury. The skull ischemic injury-induced changes in the brain transcriptome were particularly great but could recover in a short period, while the skull transcriptome variation resulting from brain ischemic injury was long-lasting. In addition, the expression of genes related to ischemic injury is also associated with pan-cell death and cancer hallmark pathways. The changes in the abundance of immune cells indicate that brain ischemic injury may disrupt its immune microenvironment for a longer time, while skull can balance the stability of immune microenvironment better. Moreover, the brain ischemic injury-related gene sets are highly correlated with a variety of tumors, especially GBM, KIRC, LGG and UVM, which carry a greater risk of death after stroke.
Conclusion: This systematic analysis not only helps us to understand the changes in gene expression profiles for both brain and skull with ischemic injury, but also reveals the association of tumor immune microenvironment and cell death with ischemic stroke.