WHOM did you contact to get the stroke strategy updated and further research initiated? No contact, then this was a waste of time and money.
Bioinformatic Analysis of Co-Expressed Differentially Expressed Genes and Potential Targets for Intracerebral and Subarachnoid Hemorrhage
ABSTRACT
BACKGROUND
Intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) are serious subtypes of hemorrhagic stroke that affect adults and have a high risk of morbidity and mortality; both share certain identical risk factors and clinical features. Recent studies have shown that secondary brain injury (SBI) following ICH and SAH is more life-threatening and lacks effective therapeutic strategies. The aim of this study is to understand the molecular pathogenesis of ICH- or SAH-induced SBI and provide insights to the potential therapeutic options.
METHODS
The original gene expression profile data of tissue microarray studies (GSE24265, GSE13353) was downloaded from the Gene Expression Omnibus (GEO) database. We identified the differentially expressed genes (DEGs) for each disease and co-DEGs between ICH and SAH. The functional enrichment analyses were then analyzed and a protein-protein interaction (PPI) network was constructed to strictly select hub genes via the maximal clique centrality (MCC) method. Additionally, immune infiltration analyses were used to identify the common differently distributed cells in both diseases. Finally, potential target microRNAs (miRNAs) and related targeted drugs were predicted for further studies. The animal model microarrays were used for external validation.
RESULTS
A total of 614 ICH-DEGs, 1272 SAH-DEGs, and 158 co-DEGs were identified in our study. The co-DEGs were significantly enriched in cytotoxicity and inflammation pathways. The top 10 hub genes (CCL20, CXCL1, CXCL3, CXCL8, CXCL16, CXCR2, CXCR4, CCR7, PF4, and PPBP) were then filtered through the PPI networks. Moreover, nTreg, Th17, and dendritic cells and monocytes and macrophages were identified as the common differentially distributed immune cells between ICH and SAH. Additionally, the target miRNAs (e.g., miR-21-5p, miR-590-5p, miR-6834-3p) and related drugs (e.g., ABX-IL8, HUMAX-IL8, Rivanicline) of hub genes were predicted.
CONCLUSIONS
This study identified a variety of key genes and their respective molecular functions involved in both ICH and SAH for better understanding of the cytotoxic and inflammatory pathogenesis of SBI. The predicted targeted miRNAs and related drugs of hub genes not only provide insights into the novel therapeutic strategies but also aid in future studies and drug discovery.
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