The potential biomarkers for the formation and development of intracranial aneurysm

J Clin Neurosci. 2020 Nov:81:270-278. doi: 10.1016/j.jocn.2020.09.072. Epub 2020 Oct 17.

Abstract

This study is aimed to understand the pathogenesis of intracranial aneurysm (IA), which has a risk of rupture and is the primary cause of subarachnoid hemorrhage. From Gene Expression Omnibus (GEO) database, GSE75436 was extracted (15 IA tissues and 15 superficial temporal artery tissues). The differentially expressed genes (DEGs) was conducted through limma package, which followed by the enrichment analysis. Combining STRING database, protein-protein interaction (PPI) network was constructed. The modules in PPI network were performed utilizing molecular complex detection (MCODE) algorithm. With Cytoscape software, the transcription factor-miRNA-target regulatory network was constructed. Finally, microarray dataset GSE54083 was downloaded (13 IA tissues and 10 superficial temporal artery tissues) for the verification test. A total of 1332 DEGs were screened in IA tissues compared with superficial temporal artery tissues. Besides, the up-regulated TNF, IL10, IL1B, and CTSS, as well as down-regulated IL6 were included in the top 20 nodes in the PPI networks. Furthermore, in the module A of up-regulated PPI network, TNF, IL10, IL1B, and VCAM1 were interact with each other. In the regulatory network, miR-29A/B/C targeted up-regulated genes. Besides, VCAM1 was implicated in the pathway of leukocyte transendothelial migration. In the verification analysis, between GSE75436 and GSE54083, there were 444 up-regulated and 543 down-regulated co-existence DEGs and 11 co-existence genes involved the Leukocyte transendothelial migration pathway. VCAM1, TNF, CTSS, IL10, IL1B, IL6, and miR-29A/B/C might be the potential biomarkers for the formation and development of IA.

Keywords: Differentially expressed genes; Intracranial aneurysm; Protein–protein interaction network; Transcription factor; microRNA.

MeSH terms

  • Biomarkers / metabolism
  • Databases, Genetic*
  • Down-Regulation / physiology
  • Gene Expression Profiling / methods*
  • Gene Regulatory Networks / physiology*
  • Humans
  • Inflammation Mediators / metabolism*
  • Intracranial Aneurysm / diagnosis
  • Intracranial Aneurysm / genetics
  • Intracranial Aneurysm / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Protein Interaction Maps / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Up-Regulation / physiology

Substances

  • Biomarkers
  • Inflammation Mediators
  • MicroRNAs
  • Transcription Factors