Identification of Potential Core Genes for the Rupture of Intracranial Aneurysms by a Bioinformatics Analysis

Abstract

Background: Previous studies, using autopsy and angiography, have shown that 3.6–6% of the population have intracranial aneurysms, and the rupture of aneurysm can lead to brain dysfunction or even death in patients.Methods: To explore potential preventional target genes for the ruptured of aneurysm, we analyze three gene expression datasets (GSE13353, GSE15629 and GSE54083) derived from the GEO database. We confirm DEGs associated with the unrupture of aneurysms by R package. DAVID version provides functional classification and annotation analyses of associated genes, including GO and KEGG pathway. PPI of these DEGs is analyzed based on the string database and visualized by Cytoscape software. DEGs are verified by qRT-PCR using samples isolated from the patients.Results: 249 overlapping DEGs, including 96 up-regulated genes and 153 down-regulated genes are screened using the Venn diagram webtool. The GO term and KEGG pathways analysis results indicate that these DEGs are mainly enriched in protein phosphorylation, apoptotic process and inflammatory response in the BP term and focal adhesion, thyroid hormone signaling pathway, ErbB signaling pathway, cytokine-cytokine receptor interaction and some disease processes in the KEGG pathways. 6 candidates are confirmed by Cytoscape software and qRT-PCR, including APP, JUN, GSK3B, ErbB2, PPBP and THBS1.Conclusions: Our data and previous studies show that ErbB2 and THBS1 are crucial to prevent aneurysm rupture, while APP, JUN, GSK3B and PPBP performs the opposite role, and further experiments are needed to verify these findings.

Mechanisms of Mitochondrial Oxidative Stress in Brain Injury: From Pathophysiology to Therapeutics

“…Multiple studies have demonstrated that neurotrophins are important for mediating neuroinflammation, apoptosis, memory capacity, and blood-brain barrier permeability. New studies are currently being conducted to further elucidate the role of neurotrophins following TBI [59].…”

Transcriptomic Studies on Intracranial Aneurysms

“…Along with the development of bioinformatic tools appeared a new type of study presenting re-analyzed data from available datasets, including expression data from the Gene Expression Omnibus (GEO). Approximately one third of these published secondary analyses utilized a single dataset [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ] and two thirds leveraged data from two to eight datasets [ 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. These studies did not provide any new additional clinical data but rather aimed to deepen the insight into molecular mechanisms of the IA pathophysiology by revealing key regulatory networks and interactions between investigated molecules.…”

A machine learning-derived gene signature for assessing rupture risk and circulatory immunopathologic landscape in patients with intracranial aneurysms

“…Mastery of these molecular pathological data will facilitate more precise individualized risk assessment in patients with IAs. In recent years, progress in high-throughput and bioinformatics technologies has provided novel opportunities for decoding the detailed molecular alterations of IAs, thereby identifying a range of potential causative genes or biomarkers (17)(18)(19). However, tissuebased biomarkers are usually difficult to apply in clinical settings because of the limited sampling.…”