CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture Risk

Background: This study used bioinformatics combined with statistical methods to identify plasma biomarkers that can predict intracranial aneurysm (IA) rupture and provide a strong theoretical basis for the search for new IA rupture prevention methods. Methods: We downloaded gene expression profiles...

Full description

Bibliographic Details
Main Authors: Dan-Dan Xu, Xiao-Qiang Liu, Zhi-Sheng Wu
Format: Article
Language:English
Published: IMR Press 2024-03-01
Series:Journal of Integrative Neuroscience
Subjects:
Online Access:https://www.imrpress.com/journal/JIN/23/3/10.31083/j.jin2303055
_version_ 1797238613717549056
author Dan-Dan Xu
Xiao-Qiang Liu
Zhi-Sheng Wu
author_facet Dan-Dan Xu
Xiao-Qiang Liu
Zhi-Sheng Wu
author_sort Dan-Dan Xu
collection DOAJ
description Background: This study used bioinformatics combined with statistical methods to identify plasma biomarkers that can predict intracranial aneurysm (IA) rupture and provide a strong theoretical basis for the search for new IA rupture prevention methods. Methods: We downloaded gene expression profiles in the GSE36791 and GSE122897 datasets from the Gene Expression Omnibus (GEO) database. Data were normalized using the “sva” R package and differentially expressed genes (DEGs) were identified using the “limma” R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used for DEG function analysis. Univariate logistic regression analysis, least absolute shrinkage and selection operator (LASSO) regression modeling, and the support vector machine recursive feature elimination (SVM-RFE) algorithm were used to identify key biomarker genes. Data from GSE122897 and GSE13353 were extracted to verify our findings. Results: Eight co-DEG mRNAs were identified in the GSE36791 and GSE122897 datasets. Genes associated with inflammatory responses were clustered in the co-DEG mRNAs in IAs. CD6 and C-C chemokine receptor 7 (CCR7) were identified as key genes associated with IA. CD6 and CCR7 were upregulated in patients with IA and their expression levels were positively correlated. There were significant differences in the infiltration of immune cells between IAs and normal vascular wall tissues (p < 0.05). A predictive nomogram was designed using this two-gene signature. Binary transformation of CD6 and CCR7 was performed according to the cut-off value to construct the receiver-operating characteristic (ROC) curve and showed a strong predictive ability of the CD6-CCR7 gene signature (p < 0.01; area under the curve (AUC): 0.90; 95% confidence interval (CI): 0.88–0.92). Furthermore, validation of this two-gene signature using the GSE122897 and GSE13353 datasets proved it to be valuable for clinical application. Conclusions: The identified two-gene signature (CD6-CCR7) for evaluating the risk of IA rupture demonstrated good clinical application value.
first_indexed 2024-04-24T17:38:26Z
format Article
id doaj.art-5990def275174167813b1442a86da123
institution Directory Open Access Journal
issn 0219-6352
language English
last_indexed 2024-04-24T17:38:26Z
publishDate 2024-03-01
publisher IMR Press
record_format Article
series Journal of Integrative Neuroscience
spelling doaj.art-5990def275174167813b1442a86da1232024-03-28T02:03:25ZengIMR PressJournal of Integrative Neuroscience0219-63522024-03-012335510.31083/j.jin2303055S0219-6352(23)00618-6CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture RiskDan-Dan Xu0Xiao-Qiang Liu1Zhi-Sheng Wu2Department of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, 362000 Quanzhou, Fujian, ChinaDepartment of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, 362000 Quanzhou, Fujian, ChinaDepartment of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, 362000 Quanzhou, Fujian, ChinaBackground: This study used bioinformatics combined with statistical methods to identify plasma biomarkers that can predict intracranial aneurysm (IA) rupture and provide a strong theoretical basis for the search for new IA rupture prevention methods. Methods: We downloaded gene expression profiles in the GSE36791 and GSE122897 datasets from the Gene Expression Omnibus (GEO) database. Data were normalized using the “sva” R package and differentially expressed genes (DEGs) were identified using the “limma” R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used for DEG function analysis. Univariate logistic regression analysis, least absolute shrinkage and selection operator (LASSO) regression modeling, and the support vector machine recursive feature elimination (SVM-RFE) algorithm were used to identify key biomarker genes. Data from GSE122897 and GSE13353 were extracted to verify our findings. Results: Eight co-DEG mRNAs were identified in the GSE36791 and GSE122897 datasets. Genes associated with inflammatory responses were clustered in the co-DEG mRNAs in IAs. CD6 and C-C chemokine receptor 7 (CCR7) were identified as key genes associated with IA. CD6 and CCR7 were upregulated in patients with IA and their expression levels were positively correlated. There were significant differences in the infiltration of immune cells between IAs and normal vascular wall tissues (p < 0.05). A predictive nomogram was designed using this two-gene signature. Binary transformation of CD6 and CCR7 was performed according to the cut-off value to construct the receiver-operating characteristic (ROC) curve and showed a strong predictive ability of the CD6-CCR7 gene signature (p < 0.01; area under the curve (AUC): 0.90; 95% confidence interval (CI): 0.88–0.92). Furthermore, validation of this two-gene signature using the GSE122897 and GSE13353 datasets proved it to be valuable for clinical application. Conclusions: The identified two-gene signature (CD6-CCR7) for evaluating the risk of IA rupture demonstrated good clinical application value.https://www.imrpress.com/journal/JIN/23/3/10.31083/j.jin2303055intracranial aneurysmbiomarkerrupturebioinformatics analysisdifferentially expressed gene
spellingShingle Dan-Dan Xu
Xiao-Qiang Liu
Zhi-Sheng Wu
CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture Risk
Journal of Integrative Neuroscience
intracranial aneurysm
biomarker
rupture
bioinformatics analysis
differentially expressed gene
title CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture Risk
title_full CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture Risk
title_fullStr CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture Risk
title_full_unstemmed CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture Risk
title_short CD6 and CCR7 as Genetic Biomarkers in Evaluating Intracranial Aneurysm Rupture Risk
title_sort cd6 and ccr7 as genetic biomarkers in evaluating intracranial aneurysm rupture risk
topic intracranial aneurysm
biomarker
rupture
bioinformatics analysis
differentially expressed gene
url https://www.imrpress.com/journal/JIN/23/3/10.31083/j.jin2303055
work_keys_str_mv AT dandanxu cd6andccr7asgeneticbiomarkersinevaluatingintracranialaneurysmrupturerisk
AT xiaoqiangliu cd6andccr7asgeneticbiomarkersinevaluatingintracranialaneurysmrupturerisk
AT zhishengwu cd6andccr7asgeneticbiomarkersinevaluatingintracranialaneurysmrupturerisk