Zhang Xianjing, Han Tingting, Xu Tengxiao, Wang Huimin, Ma Haijun
Department of Emergency Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, People's Republic of China.
Department of Radiology, Taian Maternity and Child Health Care Hospital, Taian, 271000, People's Republic of China.
Int J Gen Med. 2023 Jul 12;16:2999-3012. doi: 10.2147/IJGM.S418913. eCollection 2023.
The specific molecular mechanistic link between atherosclerotic plaques and ischemic stroke (IS) is not clear. The aim of this study is to explore the potential molecular relationship between atherosclerotic plaques and IS.
All data were downloaded from the Gene Expression Omnibus (GEO) database. Key hub differentially expressed mRNAs (DEmRNAs) related to atherosclerotic plaques and IS were identified by differential expression analysis and least absolute shrinkage and selection operator (LASSO) analysis. Subsequently, a diagnostic model was established based on the expression of key hub DEmRNAs and logistic regression. In order to understand the molecular mechanism of key hub DEmRNAs, the transcription factor (TF) regulatory network and mRNA-miRNA-lncRNA regulatory network were also constructed. In addition, functional enrichment analysis and single-sample Gene Set Enrichment Analysis (ssGSEA) analysis were also performed.
Four key hub DEmRNAs (ADCY3, CLDN7, PPM1B and RRAS2) were identified by differential expression analysis and LASSO analysis. Moreover, the diagnostic model based on four key hub DEmRNAs has excellent diagnostic accuracy. We also found that Type 1 T helper cell may be associated with IS caused by atherosclerosis based on ssGSEA analysis. In the mRNA-miRNA-lncRNA regulatory network, we found that multiple signaling axes such as RRAS2-hsa-miR-3150b-3p-ILF3-AS1, PPM1B-hsa-miR-541-5p-LINC00294, CLDN7-hsa-miR-184-LINC00467 and ADCY3-hsa-miR-488-3p-URB1-AS1 may play an important role in the progression of IS. In addition, some signaling pathways, including chemokine signaling pathway, MAPK signaling pathway and cAMP signaling pathway, may be involved in regulating IS.
The identified key molecules, signaling pathways and immune cells may help to provide a theoretical basis for exploring the relationship between atherosclerotic plaque and the progression of IS.
动脉粥样硬化斑块与缺血性卒中（IS）之间具体的分子机制联系尚不清楚。本研究旨在探讨动脉粥样硬化斑块与IS之间潜在的分子关系。
所有数据均从基因表达综合数据库（GEO）下载。通过差异表达分析和最小绝对收缩与选择算子（LASSO）分析，确定与动脉粥样硬化斑块和IS相关的关键枢纽差异表达mRNA（DEmRNAs）。随后，基于关键枢纽DEmRNAs的表达和逻辑回归建立诊断模型。为了解关键枢纽DEmRNAs的分子机制，还构建了转录因子（TF）调控网络和mRNA-miRNA-lncRNA调控网络。此外，还进行了功能富集分析和单样本基因集富集分析（ssGSEA）。
通过差异表达分析和LASSO分析确定了四个关键枢纽DEmRNAs（ADCY3、CLDN7、PPM1B和RRAS2）。此外，基于四个关键枢纽DEmRNAs的诊断模型具有优异的诊断准确性。基于ssGSEA分析，我们还发现1型辅助性T细胞可能与动脉粥样硬化引起的IS有关。在mRNA-miRNA-lncRNA调控网络中，我们发现RRAS2-hsa-miR-3150b-3p-ILF3-AS1、PPM1B-hsa-miR-541-5p-LINC00294、CLDN7-hsa-miR-184-LINC00467和ADCY3-hsa-miR-488-3p-URB1-AS1等多个信号轴可能在IS进展中发挥重要作用。此外，一些信号通路，包括趋化因子信号通路、丝裂原活化蛋白激酶（MAPK）信号通路和环磷酸腺苷（cAMP）信号通路，可能参与调节IS。
所确定的关键分子、信号通路和免疫细胞可能有助于为探索动脉粥样硬化斑块与IS进展之间的关系提供理论依据。
