IGFBP6 Is Downregulated in Unstable Carotid Atherosclerotic Plaques According to an Integrated Bioinformatics Analysis and Experimental Verification

Abstract

Aims: To investigate the differentially expressed genes (DEGs) and molecular interaction in unstable atherosclerotic carotid plaques. Methods: Gene expression datasets GSE41571, GSE118481, and E-MTAB-2055 were analyzed. Co-regulated DEGs in at least two datasets were analyzed with the enrichment of Gene Ontology Biological Process (GO-BP), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) networks, interrelationships between miRNAs/transcriptional factors, and their target genes and drug-gene interactions. The expression of notable DEGs in human carotid artery plaques and plasma was further identified. Results: The GO-BP enrichment analysis revealed that genes associated with inflammatory response, and extracellular matrix organization were altered. The KEGG enrichment analysis revealed that upregulated DEGs were enriched in the tuberculous, lysosomal, and chemokine signaling pathways, whereas downregulated genes were enriched in the focal adhesion and PI3K/Akt signaling pathway. Collagen type I alpha 2 chain ( COL1A2 ), adenylate cyclase 3 ( ADCY3 ), C-X-C motif chemokine receptor 4 ( CXCR4 ), and TYRO protein tyrosine kinase binding protein ( TYROBP ) might play crucial roles in the PPI networks. In drug–gene interactions, colony-stimulating factor-1 receptor had the most drug interactions. Insulin-like growth factor binding protein 6 ( IGFBP6 ) was markedly downregulated in unstable human carotid plaques and plasma. Under a receiver operating characteristic curve analysis, plasma IGFBP6 had a significant discriminatory power (AUC, 0.894; 95% CI, 0.810–0.977), with a cutoff value of 142.08 ng/mL. Conclusions: The genes COL1A2, ADCY3, CXCR4 , and TYROBP are promising targets for the prevention of unstable carotid plaque formation. IGFBP6 may be an important biomarker for predicting vulnerable plaques.

The clinical characteristics and prognostic value of IGFBP6 in glioma

“…Numerous reports found that genetic alteration in critical signaling pathways were significantly associated with glioma tumorigenesis, including EMT, RTK/RAS/PI(3)K, p53 and RB, ERK pathways, and so on [19,20]. IGFBP6 was involved in inhibiting IGF-II actions, promoting cell apoptosis, inducing tumor cell migration, and mediating MAPK, ERK and HIF1A related pathways [9,21,22]. Some research reported that IGFBP6 was correlated with TMZchemoresistance in GBM, and the expression of IGF-1 R and IGF2 in gliomas were associated with shorter overall survival [23].…”

Exploration and validation of related hub gene expression during SARS-CoV-2 infection of human bronchial organoids

“…The Gene Ontology (GO) database, containing three sections: biological progress (BP), cellular component (CC), molecular function (MF), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database are the most popular tools to learn about gene functions [ 19 ]. Therefore, two databases and the reference value P value < 0.05, which was considered as the significant difference, were used to further study the function of DEGs.…”

Weighted Gene Co-expression Network Analysis Identifies Crucial Genes Mediating Progression of Carotid Plaque

“…Other datasets were also employed to identify the DEGs. Liu et al (2020) analyzed GSE41571, GSE118481, and E-MTAB-2055 and discovered that JCHAIN, CXCL10, and HMOX1 were the crucial FIGURE 6 | ROC curves for NCF2, IQGAP2, and CD86. (A) The AUC for NCF2 was 0.918.…”