Atherosclerosis (AS) is the primary cause of deadly cardio-cerebro vascular diseases globally. This study aims to explore the key differentially expressed genes (DEGs), potentially serving as predictive biomarkers for AS. Microarray datasets were retrieved from the GEO database for DEGs and DE-miRNAs identification. Then biological function of DEGs were elucidated based on gene ontology (GO) and KEGG pathway enrichment analysis. The protein–protein interaction (PPI) network and DEGs-DE-miRNAs network were constructed, with emphasis on hub DEGs selection and their interconnections. Additionally, receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic precision of hub DEGs for AS. More importantly, an AS Syrian Golden hamster model was established to validate the expression levels of hub DEGs in AS. A total of 203 DEGs and 10 DE-miRNAs were screened, with six genes were chosen as hub DEGs. These DEGs were significantly enriched in AS-related biological processes and pathways, such as immune and inflammatory response, cellular response to IL-1 and TNF, positive regulation of angiogenesis, Type I diabetes mellitus, Cytokine-cytokine receptor interaction, TLR signaling pathway. Also, these DEGs and DE-miRNAs formed a closely-interacted DE-miRNAs - DEGs - KEGG pathway network. Besides, hub DEGs presented promising diagnostic potential for AS (AUC: 0.781 ∼ 0.887). In addition, the protein expression levels of TNF-α, CXCL8, CCL4, IL-1β, CCL3 and CCR8 were significantly increased in AS group Syrian Golden hamsters. The identified candidate genes TNF, CXCL8, CCL4, IL1B, CCL3 and CCR8 may have the potential to serve as prognostic biomarker in diagnosing AS.

中文翻译：

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作为与动脉粥样硬化相关的候选生物标志物的不同表达基因的鉴定和初步验证

动脉粥样硬化（AS）是全球致命心脑血管疾病的主要原因。本研究旨在探索关键的差异表达基因 (DEG)，它们有可能作为 AS 的预测生物标志物。从 GEO 数据库检索微阵列数据集，用于 DEG 和 DE-miRNA 鉴定。然后基于基因本体论（GO）和KEGG通路富集分析阐明DEG的生物学功能。构建了蛋白质-蛋白质相互作用（PPI）网络和DEGs-DE-miRNAs网络，重点是枢纽DEGs选择及其互连。此外，还进行了受试者工作特征 (ROC) 曲线分析，以评估中心 DEG 对 AS 的诊断精度。更重要的是，建立了AS叙利亚金仓鼠模型来验证AS中hub DEG的表达水平。共筛选了203个DEG和10个DE-miRNA，其中6个基因被选为中心DEG。这些DEG显着富集于AS相关的生物过程和通路，如免疫和炎症反应、细胞对IL-1和TNF的反应、血管生成的正向调节、I型糖尿病、细胞因子-细胞因子受体相互作用、TLR信号通路。此外，这些DEGs和DE-miRNAs形成了一个紧密相互作用的DE-miRNAs-DEGs-KEGG通路网络。此外，中心 DEG 对 AS 具有良好的诊断潜力（AUC：0.781 ∼ 0.887）。此外，AS组叙利亚金仓鼠TNF-α、CXCL8、CCL4、IL-1β、CCL3和CCR8的蛋白表达水平显着升高。已确定的候选基因 TNF、CXCL8、CCL4、IL1B、CCL3 和 CCR8 可能有潜力作为诊断 AS 的预后生物标志物。