缺血性脑卒中缺氧相关生物标志物的筛选

Screening for hypoxia-related biomarkers in ischemic stroke

目的研究缺氧相关基因与缺血性脑卒中之间的关系,筛选缺氧相关的分子标志物。方法首先,下载GSE16561和GSE58294数据集,以及缺氧相关基因集,筛选缺氧相关的差异表达基因,并进行功能注释。随后对这些差异表达的缺氧相关基因进行最小绝对收缩和选择算子(LASSO)回归和支持向量机算法分析,筛选缺氧相关的生物标志物,并对缺血性脑卒中组和对照组的差异免疫细胞进行分析。最后对转录因子和miRNA进行了预测。结果本研究共筛选得到13个缺氧相关的差异表达基因,这13个基因主要富集到了葡萄糖跨膜转运、单糖跨膜转运以及线粒体自噬调节等过程。基于LASSO回归和支持向量机算法,最终确定了8个缺氧相关的生物标志物,这些标志物与大部分免疫细胞之间均存在显著相关性。此外,预测到8个基因对应的209个转录因子的关系网络,以及6个基因对应的25个miRNA。结论本文最终筛选了8个缺氧相关的生物标志物,它们可能作为抑制卒中后的脑损伤的治疗靶点。此外,糖代谢和免疫机制在缺血性脑卒中的发生和发展中发挥重要作用。

Objective To investigate the relationship between hypoxia-related genes and ischemic stroke,and to screen for molecular markers related to hypoxia.Methods First,GSE16561 and GSE58294 datasets and hypoxia-related gene sets were downloaded to screen for hypoxia-related differentially expressed genes.After functional annotation,these hypoxia-related differentially expressed genes were analyzed by the least absolute shrinkage and selection operator least absolute shrinkage and selection operator(LASSO)regression and support vector machine algorithm to screen for immune-related biomarkers,and differential immune cells were analyzed between the ischemic stroke group and the control group.Finally,transcription factors and miRNAs were predicted.Results A total of 13 hypoxia-related differentially expressed genes were screened,which were enriched mainly in the processes of glucose transmembrane transport,monosaccharide transmembrane transport,and mitophagy regulation.Based on the LASSO regression and support vector machine algorithm analyses,eight hypoxia-related biomarkers were identified,which were significantly correlated with most immune cells.Furthermore,the network of 209 transcription factors corresponding to 8 genes and 25 miRNAs corresponding to 6 genes were predicted.Conclusion Eight hypoxia-related biomarkers are identified,which may be used as potential therapeutic targets for inhibiting brain injury after stroke.In addition,glucose metabolism and immune mechanisms may play an important role in the occurrence and progression of ischemic stroke.