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Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis.

ABSTRACT: Background:Because of the complex mechanisms of injury, conventional surgical treatment and early blood pressure control does not significantly reduce mortality or improve patient prognosis in cases of intracerebral hemorrhage (ICH). We aimed to identify the hub genes associated with intracerebral hemorrhage, to act as therapeutic targets, and to identify potential small-molecule compounds for treating ICH. Methods:The GSE24265 dataset, consisting of data from four perihematomal brain tissues and seven contralateral brain tissues, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) in ICH, with a fold change (FC) value of (|log2FC|) > 2 and a P-value of <0.05 set as cut-offs. The functional annotation of DEGs was performed using Gene Ontology (GO) resources, and the cell signaling pathway analysis of DEGs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), with a P-value of <0.05 set as the cut-off. We constructed a protein-protein interaction (PPI) network to clarify the interrelationships between the different DEGs and to select the hub genes with significant interactions. Next, the DEGs were analyzed using the CMap tool to identify small-molecule compounds with potential therapeutic effects. Finally, we verified the expression levels of the hub genes by RT-qPCR on the rat ICH model. Result:A total of 59 up-regulated genes and eight down-regulated genes associated with ICH were identified. The biological functions of DEGs associated with ICH are mainly involved in the inflammatory response, chemokine activity, and immune response. The KEGG analysis identified several pathways significantly associated with ICH, including but not limited to HIF-1, TNF, toll-like receptor, cytokine-cytokine receptor interaction, and chemokine molecules. A PPI network consisting of 57 nodes and 373 edges was constructed using STRING, and 10 hub genes were identified with Cytoscape software. These hub genes are closely related to secondary brain injury induced by ICH. RT-qPCR results showed that the expression of ten hub genes was significantly increased in the rat model of ICH. In addition, a CMap analysis of three small-molecule compounds revealed their therapeutic potential. Conclusion:In this study we obtained ten hub genes, such as IL6, TLR2, CXCL1, TIMP1, PLAUR, SERPINE1, SELE, CCL4, CCL20, and CD163, which play an important role in the pathology of ICH. At the same time, the ten hub genes obtained through PPI network analysis were verified in the rat model of ICH. In addition, we obtained three small molecule compounds that will have therapeutic effects on ICH, including Hecogenin, Lidocaine, and NU-1025.

SUBMITTER: Liu Z

PROVIDER: S-EPMC6816389 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis.

Liu Zhendong Z Zhang Ruotian R Chen Xin X Yao Penglei P Yan Tao T Liu Wenwu W Yao Jiawei J Sokhatskii Andrei A Gareev Ilgiz I Zhao Shiguang S

PeerJ 20191025

<h4>Background</h4>Because of the complex mechanisms of injury, conventional surgical treatment and early blood pressure control does not significantly reduce mortality or improve patient prognosis in cases of intracerebral hemorrhage (ICH). We aimed to identify the hub genes associated with intracerebral hemorrhage, to act as therapeutic targets, and to identify potential small-molecule compounds for treating ICH.<h4>Methods</h4>The GSE24265 dataset, consisting of data from four perihematomal b ...[more]

PMID: 31667013

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Project description:BackgroundAlthough epilepsy has been linked to subarachnoid hemorrhage (SAH), the underlying mechanism has not been fully elucidated. This study aimed to further explore the potential mechanisms in epilepsy and SAH through genes.MethodsGene expression profiles for subarachnoid hemorrhage (GSE36791) and epilepsy (GSE143272) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis was performed to identify the common differentially expressed genes (DEGs) to epilepsy and SAH, which were further analyzed by functional enrichment analysis. Single-sample gene set enrichment analysis (ssGSEA) and weighted correlation network analysis (WGCNA) were used to identify common module genes related to the infiltration of immune cells in epilepsy and SAH. Hub module genes were identified using a protein-protein interaction (PPI) network. Finally, the most relevant genes were obtained by taking the intersection points between the DEGs and hub module genes. We performed validation by retrospectively analyzing the RT-PCR levels of the most relevant genes in patients with pure SAH and patients with SAH complicated with epilepsy. Our experiments verified that the SAH and SAH+epilepsy groups were significantly different from the normal control group. In addition, significant differences were observed between the SAH and SAH+epilepsy groups.ResultsIn total, 159 common DEGs-85 downregulated genes and 74 upregulated genes-were identified. Functional analysis emphasized that the immune response was a common feature to epilepsy and SAH. The results of ssGSEA and WGCNA revealed changes in immunocyte recruitment and the related module genes. Finally, MMP9 and C3aR1 were identified as hub genes, and RT-PCR confirmed that the expression levels of the hub genes were higher in epilepsy and SAH samples than in normal samples.ConclusionsOur study revealed the pathogenesis of SAH complicated with epilepsy and identified hub genes that might provide new ideas for further mechanistic studies.

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Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis.

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Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis.

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