Identification of key genes and pathways in abdominal aortic aneurysm by integrated bioinformatics analysis

Abstract

Objectives: To identify key genes associated with abdominal aortic aneurysm (AAA) by integrating a microarray profile and a single-cell RNA-seq dataset. Methods: The microarray profile of GSE7084 and the single-cell RNA-seq dataset were obtained from the Gene Express Omnibus database. Differentially expressed genes (DEGs) were chosen using the R package and annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomics analysis. The hub genes were identified based on their degrees of interaction in the protein-protein interaction (PPI) network. Expression of hub genes was determined using singlecell RNA-seq analysis. Results: In total, 507 upregulated and 842 downregulated DEGs were identified and associated with AAA. The upregulated DEGs were enriched into 9 biological processes and 10 biological pathways, which were closely involved in the pathogenesis and progression of AAA. Based on the PPI network, we focused on six hub genes, four of which were novel target genes compared with the known aneurysm gene database. Using single-cell RNA-seq analysis, we explored the four genes expressed in vascular cells of AAA: CANX, CD44, DAXX, and STAT1. Conclusions: We identified key genes that may provide insight into the mechanism of AAA pathogenesis and progression and that have potential to be therapeutic targets.

Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm

“… 31–34 For identified autophagy-related genes, MCL1, HIF1A, VEGFA, PARP1, AFT4 and CANX are essential for the survival and function of vascular cells and underlie AAA. 2 , 35–39 Meanwhile, recent studies proved that EZH2 expression was regulated through m6A modification in heat stress response and cancer progression, 40 , 41 and VEGFA and PARP1 levels could be modulated in cancer cells in a m6A-dependent manner. 42 , 43 However, whether m6A modification mediated by m6A regulators could influence the expression of essential metabolism/autophagy-related genes and thus contribute to AAA formation deserves further study.…”

“… 1 Inflammation, vascular smooth muscle cell (VSMC) apoptosis, extracellular matrix degradation, and increased oxidative stress are the major histopathological features of AAA. 2 Immune inflammatory cells have been found to be in the central position of the whole process of AAA formation. 3 Recent researchers suggest that body metabolism is closely related to the initiation and development of AAA, while autophagy is an essential process mediating proper vascular function.…”

“…[31][32][33][34] For identified autophagy-related genes, MCL1, HIF1A, VEGFA, PARP1, AFT4 and CANX are essential for the survival and function of vascular cells and underlie AAA. 2,[35][36][37][38][39] Meanwhile, recent studies proved…”

Identification of potential novel biomarkers for abdominal aortic aneurysm based on comprehensive analysis of circRNA‑miRNA‑mRNA networks

“…To the best of our knowledge, few in-depth bioinformatics studies on the key circRNAs of ceRNA networks involved in AAA pathogenesis have been conducted. Although some GEO datasets in the present study have been used to perform other analyses (2,13,31,32), there are no studies exploring circRNA-miRNA-mRNA networks for AAA with these datasets. For the first time, the present study screened crucial circRNA-miRNA-mRNA axes through a series of bioinformatics tools and validated some key molecular targets.…”

Establishment of a Combined Diagnostic Model of Abdominal Aortic Aneurysm with Random Forest and Artificial Neural Network

“…The risk of AAA nearly doubles if the patient has a family genetic history [10]. Previous AAA studies have con rmed several susceptibility genes that can help diagnose AAA, including CTLA4, NKTR, CD8A, CANX, CD44, DAXX, and STAT1 [11][12][13]. Therefore, the search for AAA susceptibility genes has become an important research direction for AAA screening and diagnosis.…”