Evidence map›Paper›PMID 42417419›Full record

ArticleBioMed research international2026

Mendelian Randomization and Transcriptome Analysis Identify Ischemic Stroke Biomarkers With Putative Relevance to Cerebrospinal Fluid.

Jingwei Xiong, Jie Zhang, Xuemei Cheng, Zhiqiang Zhou, Lidong Zhang, Chunlong Chen

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Article in BioMed research international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Jingwei XiongDepartment of Anesthesiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China, nju.edu.cn.ORCID https://orcid.org/0009-0005-6042-1370
Jie ZhangDepartment of Anesthesiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China, nju.edu.cn.ORCID https://orcid.org/0000-0002-9420-0497
Xuemei ChengDepartment of Anesthesiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China, nju.edu.cn.ORCID https://orcid.org/0000-0002-6244-8578
Zhiqiang ZhouDepartment of Anesthesiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China, nju.edu.cn.ORCID https://orcid.org/0000-0003-4339-4962
Lidong ZhangDepartment of Anesthesiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China, nju.edu.cn.ORCID https://orcid.org/0000-0002-3189-9691
Chunlong ChenDepartment of Anesthesiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China, nju.edu.cn.ORCID https://orcid.org/0009-0001-7669-1595

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCirculating 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.

methodsA 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.

resultsThe 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.

conclusionCDH7, MGAT4C, and ITPKC are genetically associated and transcriptionally altered candidates derived from circulating protein-related analyses for IS, warranting further investigation.

Indexed as

BiomarkersIschemic StrokeMendelian Randomization AnalysisTranscriptomeAnimalsGene Expression ProfilingHumansMaleProtein Interaction MapsRatsBiomarkersbiomarkerscirculating proteinsischemic strokemendelian randomizationtranscriptome analysis

Identifiers

PMID42417419
PMCPMC13343476

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