Identification and validation of diagnostic biomarkers of coronary artery disease progression in type 1 diabetes via integrated computational and bioinformatics strategies

列线图 接收机工作特性 冠状动脉疾病 小桶 生物标志物 医学 基因 生物信息学 转录组 肿瘤科 生物 计算生物学 内科学 基因表达 遗传学
作者
Yufei Zhou,Chunjiang Liu,Zhongzheng Zhang,Jian Chen,Di Zhao,Linnan Li,Mingyue Tong,Gang Zhang
出处
期刊:Computers in Biology and Medicine [Elsevier]
卷期号:159: 106940-106940 被引量:2
标识
DOI:10.1016/j.compbiomed.2023.106940
摘要

Our study aimed to identify early peripheral blood diagnostic biomarkers and elucidate the immune mechanisms of coronary artery disease (CAD) progression in patients with type 1 diabetes mellitus (T1DM). Three transcriptome datasets were retrieved from the Gene Expression Omnibus (GEO) database. Gene modules associated with T1DM were selected with weighted gene co-expression network analysis. Differentially expressed genes (DEGs) between CAD and acute myocardial infarction (AMI) peripheral blood tissues were identified using limma. Candidate biomarkers were selected with functional enrichment analysis, node gene selection from a constructed protein-protein interaction (PPI) network, and 3 machine learning algorithms. Candidate expression was compared, and the receiver operating characteristic curve (ROC) and nomogram were constructed. Immune cell infiltration was assessed with the CIBERSORT algorithm. A total of 1283 genes comprising 2 modules were detected as the most associated with T1DM. In addition, 451 DEGs related to CAD progression were identified. Among them, 182 were common to both diseases and mainly enriched in immune and inflammatory response regulation. The PPI network yielded 30 top node genes, and 6 were selected using the 3 machine learning algorithms. Upon validation, 4 genes (TLR2, CLEC4D, IL1R2, and NLRC4) were recognized as diagnostic biomarkers with the area under the curve (AUC) > 0.7. All 4 genes were positively correlated with neutrophils in patients with AMI. We identified 4 peripheral blood biomarkers and provided a nomogram for early diagnosing CAD progression to AMI in patients with T1DM. The biomarkers were positively associated with neutrophils, indicating potential therapeutic targets.
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