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Bioinformatic Analysis For Discovering Intracranial Aneurysm Related Molecular Biomarkers

Posted on:2020-11-09Degree:MasterType:Thesis
Country:ChinaCandidate:X XiaFull Text:PDF
GTID:2370330623957914Subject:Outside of the surgery
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Background Intracranial aneurysm(IA)is a kind of cerebrovascular diseases which is common seen in neurosurgical department and the rupture of IA might be a leading causes of subarachnoid hemorrhage(SAH).Although IA rupture accounts for a small proportion in total stroke categories,it would result in extremely serious outcomes for the patients,with high mortality and disability rates.Moreover,the average age of ruptured IA is lower than the other types of stroke.Therefore,timely diagnosis and therapies would significantly reduce mortality and disability rate as well as decrease social and family burdens.The current therapeutic options towards IA was limited.Neurosurgery is the only option for the IA patients.However,neurosurgery would inavoidable leads to brain secondary injuries and complications,which would influence the recovery of IA patients.In recent decades,omic-related studies and applications of high-throughput technologies might discover numerous IA-related molecules,revealing the pathogenesis and progression of IA.However,we found only a minor of molecules was selected,and pathway or network studies were still limited.In another aspect,heterogenic results would be also found.Purpose In this study,we gathered and re-analyzed the mRNA-related transcriptome datasets which,were associated with IA,from Gene Expression Omnibus(GEO)database in pubmed database.Meanwhile,multiple bioinformatic tools and methods would be applied aming at discovering common molecular targets,pathways and biological functions of IA as well as exploring the pathogenesis of IA.It would provide experimental basis theoretical foundations for IA.Method We gethered trancriptome-related datasets from GEO database.Differentially expressed genes(DEGs)were analyzed by the online calculating tool GEO2 R and the parameters were set with p<0.05 and LogFC>2 or <-2.Multiplebioinformatic analyses were made respectively among datasets using DAVID database,including Gene Ontology(GO)analysis,KEGG pathway enrichment analysis and protein-protein interaction(PPI)analysis.Finally,the common DEGs were validated among 16 unruptured IA tissues and 10 normal superficial arteries by real-time PCR assay.Results A total of 17 IA related GEO datasets were available.After fintration with some conditions,twelve datasets were excluded,including 3 non-coding RNA-related datasets(GSE66239,GSE50867,GSE46336),2 cell-related datasets(GSE74452,GSE107196),2 blood-related datasets(GSE107196,GSE75434),1 dataset lack of control(GSE13353),1 undocumented dataset(GSE66238)and 1 dataset lack of expression difference(GSE75436).Five GEO datasets(GSE26969,GSE46337,GSE54083,GSE6551 and GSE15629)were finally included in our investigation,which were comprised of tow Chinese ethnic based IA datasets,one Japanese ethnic based IA dataset,one American ethnic based IA dataset and one Polish ethnic based IA dataset.However,We found no common DEGs,biological processes,molecule functions and KEGG pathway enrichments among the selected GEO dataset.Total of102 common DEGs were found between GSE26969 and GSE46337,which were two Chinese population-based datasets.Module analysis showed that IA was correlated with vascular smooth muscle contraction related genes and major histocompatibility complex(MHC)gene cluster related genes.We tested TAGLN gene expression and TPM1 gene expression between 16 unruptured IA tissues and 10 superficial artery tissues by real-time PCR.The results indicated that the expression of TAGLN was replicated and found to be decreased in the unruptured IA vessels(p=0.003),while there were no differences of TPM1 expression between the two groups(p=0.617).Conclusion(1)There were differences among mRNA-related transcriptome studies of IA,and it might contribute to the ethnic heterogeneity.(2)This bioinformatic analysis demonstrated correlations between IA and MHC gene cluster as well as vascular smooth muscle contraction related genes.(3)TAGLN was initially replicated to be decreased in the unrupture vessels of IA patients.
Keywords/Search Tags:Intracranial aneurysm, Bioinformatics, Vascular smooth muscle cell contraction, Major histocompatibility complex, TAGLN
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