Identification of potential key pathways, genes and circulating markers in the development of intracranial aneurysm based on weighted gene co-expression network analysis

Du, Guojia; Geng, Deqin; Zhou, Kai; Fan, Yandong; Su, Riqing; Zhou, Qina; Liu, Bo; Duysenbi, Serick

doi:10.1080/21691401.2020.1770264

Cited by 6 publications

(4 citation statements)

References 41 publications

(41 reference statements)

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“…Although such efforts are of great value, they do not assay the aneurysm tissue specifically for the local gene expression alterations. Small series have described the gene expression profiles from the aneurysmal domes collected as part of clipping ( 35 , 40 , 41 ); however, this type of assay is not possible for those aneurysms not amenable to open surgical treatment (similar to most fusiform vertebrobasilar aneurysms). With this manuscript, we advance the concept of endovascular biopsy and scRNAseq as a next step toward a precision medicine approach to neurovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Narsinh

McCoy

et al. 2021

Front. Neurol.

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Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa.Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis.Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα.Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.

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Section: Discussionmentioning

confidence: 99%

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Narsinh

McCoy

et al. 2021

Front. Neurol.

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“…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.…”

Section: Studies Based On Existing Datasetsmentioning

confidence: 99%

Transcriptomic Studies on Intracranial Aneurysms

Morga¹,

Pera

2023

Genes

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Intracranial aneurysm (IA) is a relatively common vascular malformation of an intracranial artery. In most cases, its presence is asymptomatic, but IA rupture causing subarachnoid hemorrhage is a life-threating condition with very high mortality and disability rates. Despite intensive studies, molecular mechanisms underlying the pathophysiology of IA formation, growth, and rupture remain poorly understood. There are no specific biomarkers of IA presence or rupture. Analysis of expression of mRNA and other RNA types offers a deeper insight into IA pathobiology. Here, we present results of published human studies on IA-focused transcriptomics.

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“…Intracranial aneurysm (IA) is a potentially devastating cerebrovascular disease characterized by the pathological dilatation of the intracerebral arterial wall to form a cystic bulge [1]. Unruptured IAs (UIAs) occur in middle-aged and elderly people in the 40-60 age group, with a prevalence of up to 3.2% [2]. A majority of patients with UIAs often have no obvious clinical manifestations and are diagnosed on examination.…”

Section: Introductionmentioning

confidence: 99%

“…However, some patients are still admitted to the hospital as an emergency with IA rupture leading to subarachnoid hemorrhage. Aneurysm rupture occurs in approximately 1% of patients with IA each year [3], resulting in a mortality rate of 30-40% and a disability rate of approximately 50% among survivors [2]. The prognosis is often poor.…”

Section: Introductionmentioning

confidence: 99%

Analysis of key genes and immune infiltration in ruptured intracranial aneurysms based on artificial neural networks and bioinformatics

Jia

Shi

et al. 2022

Preprint

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Background: Intracranial aneurysm (IA) is a potentially devastating cerebrovascular disease, and its rupture leads to subarachnoid hemorrhage with high mortality and disability rates. This study aimed to predict the potential biomarkers of ruptured intracranial aneurysms (RIAs) and explore the correlation between RIAs and immune infiltration through artificial neural networks and bioinformatics analysis.Method: Three RIA gene microarray data sets were obtained from the gene expression profile (GEO) database, with GSE13353 and GSE36791 as the training sets and GSE54083 as the validation set. Differentially expressed genes (DEGs) were obtained after the analysis. The Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Metascape databases were used for functional enrichment analysis. A random forest tree was used to screen for disease signature genes, while a neural network model was built afterward. The accuracy was also confirmed in the validation set. Finally, immune cell infiltration in the unruptured IAsand RIAs groups was analyzed using CIBERSORT.Results: A total of 27 DEGs were identified by the analysis, 1 of which was a downregulated gene and 26 were upregulated genes. The functional enrichment associated with RIAs was closely related to inflammation and immune function. Hexokinase 3, matrix metalloproteinase 9, CST7, NCF2, and uridine phosphorylase 1 were disease signature genes for RIAs and could be used as potential markers for predicting RIAs. The numbers of CD8+ T cells, CD4+ memory T cells, activated natural killer cells, macrophages M0, and neutrophils were high in the RIA group in immune cell infiltration analysis.Conclusion: The analysis revealed disease signature genes and immune cell infiltration types that predicted RIAs and had important effects on inflammatory and immune responses.

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Identification of potential key pathways, genes and circulating markers in the development of intracranial aneurysm based on weighted gene co-expression network analysis

Abstract: Duysenbi (2020) Identification of potential key pathways, genes and circulating markers in the development of intracranial aneurysm based on weighted gene coexpression network analysis,

Cited by 6 publications

References 41 publications

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Transcriptomic Studies on Intracranial Aneurysms

Analysis of key genes and immune infiltration in ruptured intracranial aneurysms based on artificial neural networks and bioinformatics

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