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基于 WGCNA 鉴定和验证促进动脉粥样硬化进展的关键基因。

Identification and verification of pivotal genes promoting the progression of atherosclerosis based on WGCNA.

机构信息

Xiamen Cardiovascular Hospital of Xiamen University, School of Medcine, Xiamen University, Xiamen, China.

Department of Neurosurgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

出版信息

Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):276-285. doi: 10.1080/21691401.2023.2203185.

Abstract

As the main pathological basis for the development of cardiovascular and cerebrovascular diseases, atherosclerosis (AS) seriously affects human health. The key targets of biological information analysis of AS can help exploit therapeutic targets. The expression data of early and progressive atherosclerotic tissues were downloaded from the Gene Expression Omnibus (GEO) database. Based on GSE28829 and GSE120521, 74 key genes were obtained through differential expression analysis and weighted correlation network analysis (WGCNA) analysis, which were mainly enriched in the regulating of inflammatory response, chemokine signalling pathway, apoptosis, lipid and AS, Toll-like receptor signalling pathway and so on according to the results of the enrichment analysis. Cytoscape software was applied to screen four pivotal genes (TYROBP, ITGB2, ITGAM and TLR2) based on PPI. The results of the correlation analysis showed that the expression level of pivotal genes was positively related to macrophages M0, and was negatively related to T cells follicular helper. In addition, the expression of ITGB2 was positively related to Tregs. In this study, bioinformatics was applied to screen pivotal genes affecting the progress of AS, which were significantly related to immune-related biological functions and signal pathways of atherosclerotic tissues and the infiltration level of immune cells. Therefore, pivotal genes were expected to become therapeutic targets for AS.

摘要

作为心血管和脑血管疾病发展的主要病理学基础,动脉粥样硬化(AS)严重影响人类健康。AS 的生物信息分析的关键靶点有助于开发治疗靶点。从基因表达综合数据库(GEO)下载了早期和进展性动脉粥样硬化组织的表达数据。基于 GSE28829 和 GSE120521,通过差异表达分析和加权相关网络分析(WGCNA)分析获得了 74 个关键基因,根据富集分析的结果,这些基因主要富集在调节炎症反应、趋化因子信号通路、细胞凋亡、脂质和 AS、Toll 样受体信号通路等。应用 Cytoscape 软件根据 PPI 筛选出四个关键基因(TYROBP、ITGB2、ITGAM 和 TLR2)。相关性分析结果表明,关键基因的表达水平与巨噬细胞 M0 呈正相关,与滤泡辅助性 T 细胞呈负相关。此外,ITGB2 的表达与 Tregs 呈正相关。在这项研究中,应用生物信息学筛选了影响 AS 进展的关键基因,这些基因与动脉粥样硬化组织的免疫相关生物学功能和信号通路以及免疫细胞的浸润水平显著相关。因此,关键基因有望成为 AS 的治疗靶点。

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