Analysis Of The Difference Expression Of Serum Protein Related To The Risk Of Intracranial Aneurysm Rupture

Objective:Label-free Quantitative Proteomics was used to identify differentially expressed proteins in the serum of patients with intracranial aneurysms,and bioinformatics was used to analyze the role of differentially expressed proteins in the pathogenesis of intracranial aneurysm rupture,so as to screen and analyze the differential proteins related to intracranial aneurysm rupture for further study.Methods:Blood samples of 101 patients with intracranial aneurysms were collected,including 49 patients with unruptured intracranial aneurysms and 52 patients with ruptured intracranial aneurysms.The serum samples were extracted for protein extraction and enzymolysis.Label-free Quantitative Proteomics method was used to analyze the proteins from experimental group versus the control group.Differentially expressed proteins were selected by LC-MS with the aid of the protein profiling software maxquant and MS database.After screening the differentially expressed proteins,bioinformatics analysis was used to analyze them.Differentially expressed proteins closely related to the mechanism of intracranial aneurysm rupture were selected as target proteins.The candidate peptides corresponding to the target proteins were validated by PRM quantitative analysis,and the expression differences of the target proteins between the two groups of samples were calculated.In addition,proteins with significant differences between the two groups that were consistent with the changes in the results of label-free quantitative proteomics were selected as candidates,and then the effects of the candidate proteins on the occurrence and development of the disease were analyzed.Results:1.A total of 35 significantly differentially expressed proteins(fold change > 1.3,P < 0.05)were identified through label free,of which 5 were up-regulated and 30 down regulated.GO analysis showed that differentially expressed proteins were mainly distributed outside the cells and were mainly involved in the process of enzyme inhibitor activity.KEGG pathway enrichment analysis suggested that the differential proteins were mainly involved in the complement and coagulation cascades,cholesterol metabolism,glycosylphosphatidylinositol(GPI)-anchor biosynthesis,and peroxisome proliferator activated receptor(PPARγ)signal transduction pathways,in which the complement and coagulation cascades pathways are important in the development and progression of intracranial aneurysm rupture 2.After screening 35 differentially expressed proteins,5 differentially expressed proteins with high correlation in the pathogenesis of intracranial aneurysm rupture were selected for PRM verification.Finally,there were four differential proteins with the same trend in Label-free Quantitative Proteomics and PRM quantitative results,and the differences were statistically significant.They were gelsolin,histidine rich glycoprotein,alpha-2-antiplasmin,alpha-2-hs-glycoprotein.The PPI network of protein-protein interaction showed that AHSG protein had high correlation with other proteins and reliable interaction.AHSG protein was expressed in PPAR γ signaling pathway and inflammatory reaction,which is closely related to the pathogenesis of intracranial aneurysms.AHSG may be used as a candidate protein.Conclusion:AHSG protein is involved in the PPAR γ signaling pathway and inflammatory reaction in the pathogenesis of intracranial aneurysm rupture.The results of label free and PRM are consistent.The expression of AHSG protein was down regulated in RIA group with statistical difference.AHSG protein may play a role in inhibiting the rupture of intracranial aneurysms,which has further research and analysis value.