鉴定脑出血中与衰老相关的生物标记物和调控网络

IF 1.1 4区 医学 Q4 CLINICAL NEUROLOGY
Yan Wang, Ling Chen
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引用次数: 0

摘要

目的:脑出血(ICH)是一种严重的神经系统疾病,具有重大的社会影响。细胞衰老在 ICH 发病机制中起着关键作用。本研究旨在鉴定 ICH 中与衰老相关的生物标记物,以用于诊断和治疗:方法:下载基因表达总库(Gene Expression Omnibus)中 GSE24265 的原始数据。衰老相关基因来自 CellAge。对 ICH 患者和对照组进行差异基因分析。ICH 差异表达基因与衰老相关基因的交叉点为衰老相关的 ICH 基因。进行了基因本体和京都基因与基因组百科全书的富集分析。通过检索相互作用基因的搜索工具构建了蛋白质-蛋白质相互作用网络。利用 miRWalk2.0 数据库预测了针对 ICH 生物标志物的 microRNA。基于句子的文本挖掘数据库揭示了转录调控关系,用于预测调控已识别生物标志物的转录因子:结果:发现了 13 个与衰老相关的 ICH 基因。结果:发现了 13 个与衰老相关的 ICH 基因,它们主要富集于血管生成的正向调控和糖尿病并发症中的高级糖化终产物-AGE 受体信号通路。GSE149317 数据集和接收器操作特征分析的验证结果表明,Caveolin 1、C-X-C Motif Chemokine Ligand 1、ETS 原癌基因 1、转录因子和 Serpin 家族 E 成员 1 是潜在的 ICH 生物标志物。单样本基因组富集分析显示,ICH 患者的 2 型 T 辅助细胞 2_细胞、Treg 细胞以及抗原递呈细胞协同刺激等免疫功能增加。包括has-miR-6728-3p在内的14种microRNA被预测为可调控这些生物标志物,PPARG、RARA、HMGA1和NFKB1等转录因子被确定为ICH生物标志物的潜在调控因子:结论:Caveolin 1、C-X-C Motif Chemokine Ligand 1、ETS 原癌基因 1、转录因子和 Serpin 家族 E 成员 1 可作为有价值的 ICH 生物标志物。以这些基因为靶标可有助于 ICH 的预防和治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of Senescence-Related Biomarkers and Regulatory Networks in Intracerebral Hemorrhage.

Objectives: Intracerebral hemorrhage (ICH) is a severe neurological disorder with substantial societal implications. Cellular senescence plays a critical role in ICH pathogenesis. This study aims to identify senescence-related biomarkers in ICH for diagnostic and therapeutic purposes.

Methods: Raw data from GSE24265 in Gene Expression Omnibus was downloaded. Senescence-related genes were acquired from CellAge. Differential gene analysis was done between patients with ICH and controls. The intersection of ICH differentially expressed genes and senescence-related genes for senescence-related ICH genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Protein-protein interaction network was constructed through the Search Tool for the Retrieval of Interacting Genes. Single sample gene set enrichment analysis was done for immune cell infiltration and function evaluation in control and ICH groups. miRWalk2.0 database was used for microRNA predictions targeting ICH biomarkers. Transcriptional regulatory relationships unraveled by sentence-based text mining database was employed to predict transcription factors regulating identified biomarkers.

Results: Thirteen senescence-related ICH genes were identified. They were primarily enriched in the positive regulation of angiogenesis and the Advanced Glycation End Product -Receptor for AGE signaling pathway in diabetic complications. Validation in the GSE149317 data set and receiver operating characteristic analysis highlighted Caveolin 1, C-X-C Motif Chemokine Ligand 1, ETS proto-oncogene 1, transcription factor, and Serpin Family E Member 1 as potential ICH biomarkers. Single sample gene set enrichment analysis revealed increased Type 2 T helper cell 2_cells, Treg cells, and immune functions like Antigen-presenting cells_co_stimulation in patients with ICH. Fourteen microRNA, including has-miR-6728-3p, were predicted to regulate these biomarkers. transcription factors such as PPARG, RARA, HMGA1, and NFKB1 were identified as potential regulators of the ICH biomarkers.

Conclusion: Caveolin 1, C-X-C Motif Chemokine Ligand 1, ETS proto-oncogene 1, transcription factor, and Serpin Family E Member 1 may serve as valuable biomarkers in ICH. Targeting these genes could contribute to ICH prevention and treatment.

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来源期刊
Neurologist
Neurologist 医学-临床神经学
CiteScore
1.90
自引率
0.00%
发文量
151
审稿时长
2 months
期刊介绍: The Neurologist publishes articles on topics of current interest to physicians treating patients with neurological diseases. The core of the journal is review articles focusing on clinically relevant issues. The journal also publishes case reports or case series which review the literature and put observations in perspective, as well as letters to the editor. Special features include the popular "10 Most Commonly Asked Questions" and the "Patient and Family Fact Sheet," a handy tear-out page that can be copied to hand out to patients and their caregivers.
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