Identification of key genes for cuproptosis in carotid atherosclerosis.

IF 2.8 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Frontiers in Cardiovascular Medicine Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI:10.3389/fcvm.2024.1471153

Xize Wu, Jian Kang, Xue Pan, Chentian Xue, Jiaxiang Pan, Chao Quan, Lihong Ren, Lihong Gong, Yue Li

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引用次数: 0

Abstract

Background: Atherosclerosis is a leading cause of cardiovascular disease worldwide, while carotid atherosclerosis (CAS) is more likely to cause ischemic cerebrovascular events. Emerging evidence suggests that cuproptosis may be associated with an increased risk of atherosclerotic cardiovascular disease. This study aims to explore the potential mechanisms linking cuproptosis and CAS.

Methods: The GSE100927 and GSE43292 datasets were merged to screen for CAS differentially expressed genes (DEGs) and intersected with cuproptosis-related genes to obtain CAS cuproptosis-related genes (CASCRGs). Unsupervised cluster analysis was performed on CAS samples to identify cuproptosis molecular clusters. Weighted gene co-expression network analysis was performed on all samples and cuproptosis molecule clusters to identify common module genes. CAS-specific DEGs were identified in the GSE100927 dataset and intersected with common module genes to obtain candidate hub genes. Finally, 83 machine learning models were constructed to screen hub genes and construct a nomogram to predict the incidence of CAS.

Results: Four ASCRGs (NLRP3, SLC31A2, CDKN2A, and GLS) were identified as regulators of the immune infiltration microenvironment in CAS. CAS samples were identified with two cuproptosis-related molecular clusters with significant biological function differences based on ASCRGs. 220 common module hub genes and 1,518 CAS-specific DEGs were intersected to obtain 58 candidate hub genes, and the machine learning model showed that the Lasso + XGBoost model exhibited the best discriminative performance. Further external validation of single gene differential analysis and nomogram identified SGCE, PCDH7, RAB23, and RIMKLB as hub genes; SGCE and PCDH7 were also used as biomarkers to characterize CAS plaque stability. Finally, a nomogram was developed to assess the incidence of CAS and exhibited satisfactory predictive performance.

Conclusions: Cuproptosis alters the CAS immune infiltration microenvironment and may regulate actin cytoskeleton formation.

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识别颈动脉粥样硬化中的杯突症关键基因。

背景：动脉粥样硬化是导致全球心血管疾病的主要原因，而颈动脉粥样硬化（CAS）更容易导致缺血性脑血管事件。新的证据表明，杯状红细胞增多症可能与动脉粥样硬化性心血管疾病风险的增加有关。本研究旨在探索杯突与 CAS 的潜在关联机制：方法：合并 GSE100927 和 GSE43292 数据集，筛选 CAS 差异表达基因（DEGs），并与杯突症相关基因交叉，得到 CAS 杯突症相关基因（CASCRGs）。对 CAS 样本进行无监督聚类分析，以确定杯突分子聚类。对所有样本和杯突症分子簇进行加权基因共表达网络分析，以确定共同的模块基因。在 GSE100927 数据集中确定了中科院特异性 DEGs，并将其与常见模块基因交叉，以获得候选枢纽基因。最后，构建了83个机器学习模型来筛选枢纽基因，并构建了预测CAS发病率的提名图：结果：4个ASCRGs（NLRP3、SLC31A2、CDKN2A和GLS）被确定为CAS免疫浸润微环境的调节因子。根据 ASCRGs，CAS 样本被鉴定出两个具有显著生物学功能差异的杯突症相关分子集群。对220个常见模块枢纽基因和1,518个CAS特异性DEGs进行交叉分析，得到58个候选枢纽基因，机器学习模型显示，Lasso + XGBoost模型表现出最佳的判别性能。单基因差异分析和提名图的进一步外部验证确定了 SGCE、PCDH7、RAB23 和 RIMKLB 为中枢基因；SGCE 和 PCDH7 还被用作表征 CAS 斑块稳定性的生物标记物。最后，研究人员绘制了评估CAS发病率的提名图，其预测效果令人满意：Cuproptosis改变了CAS免疫浸润的微环境，并可能调控肌动蛋白细胞骨架的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Cardiovascular Medicine Medicine-Cardiology and Cardiovascular Medicine

CiteScore

3.80

自引率

11.10%

发文量

3529

审稿时长

14 weeks

期刊介绍： Frontiers? Which frontiers? Where exactly are the frontiers of cardiovascular medicine? And who should be defining these frontiers? At Frontiers in Cardiovascular Medicine we believe it is worth being curious to foresee and explore beyond the current frontiers. In other words, we would like, through the articles published by our community journal Frontiers in Cardiovascular Medicine, to anticipate the future of cardiovascular medicine, and thus better prevent cardiovascular disorders and improve therapeutic options and outcomes of our patients.