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脑缺血再灌注中血管生成相关生物标志物和治疗靶点的生物信息学鉴定

Bioinformatics Identification of angiogenesis-related biomarkers and therapeutic targets in cerebral ischemia-reperfusion.

作者信息

Wu Yong-Hong, Sun Jing, Huang Jun-Hua, Lu Xiao-Yun

机构信息

Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, Shanxi Province, China.

School of Medical Technology & Institute of Basic Translational Medicine, Xi'an Medical University, Xi'an, 710021, Shanxi Province, China.

出版信息

Sci Rep. 2024 Dec 30;14(1):32096. doi: 10.1038/s41598-024-83783-9.

Abstract

Promoting vascular endothelial cell regeneration can enhance recovery from cerebral ischemia reperfusion injury (CIRI), but there is a lack of bioinformatic studies on angiogenesis-related biomarkers in CIRI. In this study, we utilized the GSE97537 and GSE61616 datasets from GEO to identify 181 angiogenesis-related genes (ARGs) and analyzed differentially expressed genes (DEGs) between CIRI and control groups. We converted ARGs to 169 rat homologues and intersected them with DEGs to find DE-ARGs. RF and XGBoost models were employed to identify five biomarkers (Stat3, Hmox1, Egfr, Col18a1, Ptgs2) and conducted GSEA on these biomarkers, revealing their enrichment in pathways such as ECM-receptor interaction and hematopoietic cell lineage. We also analyzed the immune microenvironment, finding significant differences in 21 immune cells between CIRI and control groups. Furthermore, we constructed lncRNA-miRNA-mRNA networks and drug-gene networks. Finally, biomarker expression was compared between the CIRI and control groups by qRT-PCR in tissue and blood samples. Overall, our bioinformatic exploration of angiogenesis-related biomarkers in CIRI provides new insights for the diagnosis and treatment of CIRI.

摘要

促进血管内皮细胞再生可增强脑缺血再灌注损伤(CIRI)后的恢复,但目前缺乏关于CIRI中血管生成相关生物标志物的生物信息学研究。在本研究中,我们利用来自GEO的GSE97537和GSE61616数据集,鉴定出181个血管生成相关基因(ARG),并分析了CIRI组与对照组之间的差异表达基因(DEG)。我们将ARG转化为169个大鼠同源基因,并与DEG进行交叉分析以找到差异表达的血管生成相关基因(DE-ARG)。采用随机森林(RF)和极端梯度提升(XGBoost)模型鉴定出5个生物标志物(Stat3、Hmox1、Egfr、Col18a1、Ptgs2),并对这些生物标志物进行基因集富集分析(GSEA),发现它们在细胞外基质-受体相互作用和造血细胞谱系等通路中富集。我们还分析了免疫微环境,发现CIRI组与对照组之间21种免疫细胞存在显著差异。此外,我们构建了lncRNA-miRNA-mRNA网络和药物-基因网络。最后,通过qRT-PCR比较了CIRI组与对照组在组织和血液样本中的生物标志物表达。总体而言,我们对CIRI中血管生成相关生物标志物的生物信息学探索为CIRI的诊断和治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/492f/11685884/f7adf21a240b/41598_2024_83783_Fig2_HTML.jpg

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