Mendelian Randomization and Transcriptome Analysis Identify Ischemic Stroke Biomarkers With Putative Relevance to Cerebrospinal Fluid.
Background: Circulating proteins have been associated with the pathogenesis of ischemic stroke (IS), yet its biomarkers remain underutilized. Using plasma protein GWAS data with putative relevance to CSF, this study integrated mendelian randomization (MR) and transcriptomics to identify potential IS...
| Publicado en: | BioMed Research International Vol. 2026; pp. 1 - 14 |
|---|---|
| Autores principales: | , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
7/8/2026
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=195176693&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 195176693 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 7/8/2026 vid: 2026 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 195176693 195176693 195176693 10.1155/bmri/2880611 195176693 ppf: 1 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: Mendelian Randomization and Transcriptome Analysis Identify Ischemic Stroke Biomarkers With Putative Relevance to Cerebrospinal Fluid. aug: au: Xiong, Jingwei Zhang, Jie Cheng, Xuemei Zhou, Zhiqiang Zhang, Lidong Chen, Chunlong Banerjee, Baisakhi affil: Department of Anesthesiology, , Jinling Hospital, , Affiliated Hospital of Medical School, , Nanjing University, , Nanjing, Jiangsu, , China, nju.edu.cn sug: subj: Ischemic Stroke Familial and Genetic Biological Markers Blood Biological Markers Cerebrospinal Fluid Mendelian Randomization Transcriptomes Gene Expression Profiling Animal Studies Rats In Vivo Studies Descriptive Statistics ROC Curve Spearman's Rank Correlation Coefficient T-Tests Post Hoc Analysis Wilcoxon Rank Sum Test Confidence Intervals Data Analysis Software Individualized Medicine Bioinformatics Machine Learning Signal Transduction Calcium Genistein Therapeutic Use Pioglitazone Therapeutic Use Immunohistochemistry Reverse Transcriptase Polymerase Chain Reaction ab: Background: Circulating proteins have been associated with the pathogenesis of ischemic stroke (IS), yet its biomarkers remain underutilized. Using plasma protein GWAS data with putative relevance to CSF, this study integrated mendelian randomization (MR) and transcriptomics to identify potential IS biomarkers. Methods: A two‐sample MR analysis was undertaken to determine the genetic association between circulating protein levels and IS. The identification of differentially expressed genes (DEGs) in the GSE268634 and GSE262257 datasets was carried out via the transcriptomic analysis. Candidate biomarkers overlapping MR‐derived genes (MRGs) and DEGs underwent functional enrichment, protein‐protein interaction (PPI), and machine learning (LASSO/SVM‐RFE) screening. Biomarker mechanisms were assessed via gene set enrichment analysis (GSEA), immune infiltration, and hypothesis‐generating drug prediction. The validation included RT‐qPCR and immunohistochemistry in MCAO/R rats. Results: The MR analysis identified 157 circulating protein‐related MRGs with suggestive genetic associations with IS. Transcriptomics identified 4144 DEGs, and 46 overlapping with MRGs. Functional enrichment highlighted their roles in cell adhesion and immune responses. Machine learning identified six candidate biomarkers, among which CDH7, MGAT4C, and ITPKC exhibited both high diagnostic accuracy (AUC > 0.7) and consistently differential expression, and were therefore prioritized as putative biomarkers. GSEA revealed that CDH7 and MGAT4C were positively correlated, whereas ITPKC was negatively correlated with the calcium signaling pathway. Immune infiltration analysis showed that CDH7 and MGAT4C were negative, whereas ITPKC was positively correlated with immune cells. Computationally predicted drugs including genistein and pioglitazone may alleviate IS damage, though this requires experimental confirmation. RT‐qPCR and immunohistochemistry indicated markedly high CDH7 and MGAT4C expression, whereas low ITPKC expression was in MCAO/R rats. Conclusion: CDH7, MGAT4C, and ITPKC are genetically associated and transcriptionally altered candidates derived from circulating protein‐related analyses for IS, warranting further investigation. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|