Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou 510120, China.
J Zhejiang Univ Sci B. 2021;22(9):718-732. doi: 10.1631/jzus.B2000544.
This study aimed to uncover underlying mechanisms and promising intervention targets of heart failure (HF)-related stroke. HF-related dataset GSE42955 and stroke-related dataset GSE58294 were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and hub genes. Gene Ontology (GO) and pathway enrichment analyses were performed on genes in the key modules. Genes in HF- and stroke-related key modules were intersected to obtain common genes for HF-related stroke, which were further intersected with hub genes of stroke-related key modules to obtain key genes in HF-related stroke. Key genes were functionally annotated through GO in the Reactome and Cytoscape databases. Finally, key genes were validated in these two datasets and other datasets. HF- and stroke-related datasets each identified two key modules. Functional enrichment analysis indicated that protein ubiquitination, Wnt signaling, and exosomes were involved in both HF- and stroke-related key modules. Additionally, ten hub genes were identified in stroke-related key modules and 155 genes were identified as common genes in HF-related stroke. OTU deubiquitinase with linear linkage specificity() and nuclear factor interleukin 3-regulated() were determined to be the key genes in HF-related stroke. Through functional annotation, was involved in protein ubiquitination and Wnt signaling, and was involved in DNA binding and transcription. Importantly, and were also validated to be differentially expressed in all HF and stroke groups. Protein ubiquitination, Wnt signaling, and exosomes were involved in HF-related stroke. and may play a key role in HF-related stroke through regulating these processes, and thus serve as promising intervention targets.
本研究旨在揭示心力衰竭(HF)相关卒中的潜在机制和有前途的干预靶点。从基因表达综合数据库(GEO)中获取与 HF 相关的数据集 GSE42955 和与卒中相关的数据集 GSE58294。通过加权基因共表达网络分析(WGCNA)鉴定关键模块和枢纽基因。对关键模块中的基因进行基因本体论(GO)和通路富集分析。将 HF 和卒中相关关键模块中的基因进行交集,得到与 HF 相关卒中相关的共同基因,进一步与卒中相关关键模块中的枢纽基因进行交集,得到 HF 相关卒中的关键基因。通过 Reactome 和 Cytoscape 数据库中的 GO 对关键基因进行功能注释。最后,在这两个数据集和其他数据集中验证关键基因。HF 和卒中相关数据集各鉴定出两个关键模块。功能富集分析表明,蛋白质泛素化、Wnt 信号和外泌体均参与 HF 和卒中相关关键模块。此外,在卒中相关关键模块中鉴定出 10 个枢纽基因,在 HF 相关卒中中共鉴定出 155 个共同基因。OTU 去泛素化酶具有线性连接特异性()和核因子白细胞介素 3 调节()被确定为 HF 相关卒中的关键基因。通过功能注释,参与蛋白质泛素化和 Wnt 信号,参与 DNA 结合和转录。重要的是,和也在所有 HF 和卒中组中被验证为差异表达。蛋白质泛素化、Wnt 信号和外泌体均参与 HF 相关卒中。和可能通过调节这些过程在 HF 相关卒中中发挥关键作用,因此可作为有前途的干预靶点。