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Bioinformatics Analysis Reveals HIST1H2BH as a Novel Diagnostic Biomarker for Atrial Fibrillation-Related Cardiogenic
Wenbing Jiang1, Lelin Jiang2, Xiaoli Zhao3
1Department of Cardiology, Wenzhou Integrated Traditional Chinese and Western Medicine Hospital, No.75 Jinxiu Road, Lucheng District, Wenzhou, 325000, Zhejiang Province, People's Republic of China. jiangwb919@wmu.edu.cn.
Insights
Atrial fibrillation (AF) can lead to stroke. Researchers identified HIST1H2BH as a key biomarker for diagnosing AF-related cerebral embolism (AF-CE), offering new diagnostic potential.
Area of Science:
- Biomarker Discovery
- Genomics
- Cardiovascular Research
Background:
- Atrial fibrillation (AF) is a major risk factor for cerebral embolism.
- Current diagnostic methods for AF-related cerebral embolism (AF-CE) require improvement.
- Identifying novel biomarkers is crucial for early detection and management of AF-CE.
Purpose of the Study:
- To discover novel diagnostic biomarkers for atrial fibrillation-related cerebral embolism (AF-CE).
- To analyze gene expression data from AF and stroke patient cohorts.
- To validate potential biomarkers using meta-analysis and statistical modeling.
Main Methods:
- Examination of multiple Gene Expression Omnibus (GEO) datasets.
- Meta-analysis of RNA sequencing data to identify differentially expressed genes.
- LASSO regression and Receiver Operating Characteristic (ROC) curve analysis for biomarker selection and validation.
- Gene Ontology (GO) and KEGG pathway enrichment analysis.
- Protein-protein interaction (PPI) network analysis.
Main Results:
- Differential gene expression analysis identified 16 upregulated and 4 downregulated genes in stroke patient blood samples.
- Meta-analysis confirmed varied expression in eight genes; LASSO regression pinpointed five key genes.
- HIST1H2BH was identified as a characteristic gene for AF-CE, with high diagnostic accuracy confirmed by ROC analysis.
- Active pathways included integrin signaling, platelet activation, ECM interactions, and PI3K-Akt.
- HIST1H2BH showed interaction with ITGA2B and links with NK cells and eosinophils.
Conclusions:
- HIST1H2BH is a promising diagnostic biomarker for atrial fibrillation-related cerebral embolism (AF-CE).
- This biomarker may influence platelet activation and thrombus formation, contributing to embolism.
- Further research into HIST1H2BH's role can enhance AF-CE diagnosis and therapeutic strategies.
Abstract:
Atrial fibrillation (AF) is a significant precursor to cerebral embolism. Our study sought to unearth new diagnostic biomarkers for atrial fibrillation-related cerebral embolism (AF-CE) by meticulously examining multiple GEO datasets and meta-analysis. The gene expression omnibus (GEO) database provided RNA sequencing data associated with AF and stroke. We began by pinpointing genes with varied expressions in AF-CE patient blood samples. A meta-analysis was subsequently undertaken using several RNA sequencing datasets to verify these genes. LASSO regression discerned key genes for AF-CE, with their diagnostic prowess verified through ROC curve examination. Active signaling pathways within stroke patients were discerned via GO and KEGG enrichment, with PPI interactions detailing gene interplay. Differential gene analysis revealed an upregulation of sixteen genes and a downregulation of four in stroke patient blood samples. Eight genes showcased varied expression in the meta-analysis. LASSO regression zeroed in on five of these, culminating in HIST1H2BH's identification as a characteristic gene. HIST1H2BH's prowess in predicting AF-CE was confirmed through ROC. Integrin signaling, platelet activation, ECM interactions, and the PI3K-Akt pathway were found active in stroke victims. HIST1H2BH's interaction with the notably upregulated ITGA2B was spotlighted by PPI. Additionally, HIST1H2BH exhibited links with NK cells and eosinophils. HIST1H2BH emerges as an insightful diagnostic beacon for AF-CE. Its presence, post AF, potentially modulates pathways, accentuating platelet activation and consequent thrombus generation, leading to cerebral embolism.
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