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基于 WGCNA 和机器学习算法鉴定心房颤动和稳定型冠状动脉疾病的潜在生物标志物。

Identification of potential biomarkers for atrial fibrillation and stable coronary artery disease based on WGCNA and machine algorithms.

机构信息

Department of Cardiology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China.

Shandong University, Jinan, 250012, China.

出版信息

BMC Cardiovasc Disord. 2024 Aug 2;24(1):401. doi: 10.1186/s12872-024-04062-z.

Abstract

BACKGROUND

Patients with atrial fibrillation (AF) often have coronary artery disease (CAD), but the biological link between them remains unclear. This study aims to explore the common pathogenesis of AF and CAD and identify common biomarkers.

METHODS

Gene expression profiles for AF and stable CAD were downloaded from the Gene Expression Omnibus database. Overlapping genes related to both diseases were identified using weighted gene co-expression network analysis (WGCNA), followed by functional enrichment analysis. Hub genes were then identified using the machine learning algorithm. Immune cell infiltration and correlations with hub genes were explored, followed by drug predictions. Hub gene expression in AF and CAD patients was validated by real-time qPCR.

RESULTS

We obtained 28 common overlapping genes in AF and stable CAD, mainly enriched in the PI3K-Akt, ECM-receptor interaction, and relaxin signaling pathway. Two hub genes, COL6A3 and FKBP10, were positively correlated with the abundance of MDSC, plasmacytoid dendritic cells, and regulatory T cells in AF and negatively correlated with the abundance of CD56dim natural killer cells in CAD. The AUCs of COL6A3 and FKBP10 were all above or close to 0.7. Drug prediction suggested that collagenase clostridium histolyticum and ocriplasmin, which target COL6A3, may be potential drugs for AF and stable CAD. Additionally, COL6A3 and FKBP10 were upregulated in patients with AF and CAD.

CONCLUSION

COL6A3 and FKBP10 may be key biomarkers for AF and CAD, providing new insights into the diagnosis and treatment of this disease.

摘要

背景

心房颤动(AF)患者常伴有冠状动脉疾病(CAD),但其生物学联系尚不清楚。本研究旨在探讨 AF 和 CAD 的共同发病机制,寻找共同的生物标志物。

方法

从基因表达综合数据库(Gene Expression Omnibus database)中下载 AF 和稳定 CAD 的基因表达谱。使用加权基因共表达网络分析(WGCNA)鉴定与两种疾病相关的重叠基因,然后进行功能富集分析。接着使用机器学习算法识别关键基因。探索免疫细胞浸润与关键基因的相关性,并进行药物预测。通过实时 qPCR 验证 AF 和 CAD 患者中关键基因的表达。

结果

我们在 AF 和稳定 CAD 中获得了 28 个共同重叠基因,主要富集于 PI3K-Akt、ECM-受体相互作用和松弛素信号通路。COL6A3 和 FKBP10 这两个关键基因与 AF 中髓系来源抑制细胞、浆细胞样树突状细胞和调节性 T 细胞的丰度呈正相关,与 CAD 中 CD56dim 自然杀伤细胞的丰度呈负相关。COL6A3 和 FKBP10 的 AUC 值均高于或接近 0.7。药物预测提示,针对 COL6A3 的胶原酶组织溶菌素和 ocriplasmin 可能是 AF 和稳定 CAD 的潜在药物。此外,COL6A3 和 FKBP10 在 AF 和 CAD 患者中均上调。

结论

COL6A3 和 FKBP10 可能是 AF 和 CAD 的关键生物标志物,为该疾病的诊断和治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8d8/11295489/2a3411e7a3d9/12872_2024_4062_Fig1_HTML.jpg

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