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<p>Developing cost-effective, noninvasive biomarker-based tests could transform moyamoya disease (MMD) management. This study aimed to identify clinically relevant cerebrospinal fluid (CSF) biomarkers through comprehensive proteomic screening in a large MMD cohort. CSF protein profiles from 104 MMD patients and 14 non-tumorous hydrocephalus patients were analyzed via liquid chromatography-tandem mass spectrometry. Enrichment analysis was conducted on canonical pathways and differentially expressed proteins (DEPs). The protein–protein interaction network data included all proteins involved in canonical pathways. Potential markers were validated via ELISA. Weighted gene coexpression network analysis (WGCNA) revealed clinical factor-related modules. We identified 2463 proteins, and 2307 were quantified in at least one sample. A total of 321 significant DEPs were identified, with 8 proteins upregulated and 11 proteins downregulated in MMD samples. ELISA confirmed the increased expression of ALB and SLITRK1. WGCNA revealed seven modules correlated with clinical factors, linking preoperative cerebral infarction to the module eigengene (ME) red module and favorable modified Rankin scale scores to the MEblack module. BASP1 and LDHA were significantly upregulated in MEred, whereas CD9 and EMILIN1 were upregulated in MEblack. Our findings shed light on the proteomics of CSF from MMD patients, identifying potential novel biomarkers such as SLITRK1 and markers of preoperative cerebral infarction (BASP1, LDHA) and clinical outcome (CD9, EMILIN1). These markers have potential as new diagnostic and therapeutic targets for MMD.</p>

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Identification of Biomarkers Related to the Pathogenesis and Prognosis of Pediatric Moyamoya Disease Via Cerebrospinal Fluid Proteomics

  • 期刊论文

  • 发表日期：

    2025年10月1日

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  • Youngbo Shim,
  • Seung Ah Choi,
  • Kisoon Dan,
  • Eun Jung Koh,
  • Saehim Ha,
  • Ji Hoon Phi,
  • Joo Whan Kim,
  • Dohyun Han,
  • Seung-Ki Kim

摘要

Developing cost-effective, noninvasive biomarker-based tests could transform moyamoya disease (MMD) management. This study aimed to identify clinically relevant cerebrospinal fluid (CSF) biomarkers through comprehensive proteomic screening in a large MMD cohort. CSF protein profiles from 104 MMD patients and 14 non-tumorous hydrocephalus patients were analyzed via liquid chromatography-tandem mass spectrometry. Enrichment analysis was conducted on canonical pathways and differentially expressed proteins (DEPs). The protein–protein interaction network data included all proteins involved in canonical pathways. Potential markers were validated via ELISA. Weighted gene coexpression network analysis (WGCNA) revealed clinical factor-related modules. We identified 2463 proteins, and 2307 were quantified in at least one sample. A total of 321 significant DEPs were identified, with 8 proteins upregulated and 11 proteins downregulated in MMD samples. ELISA confirmed the increased expression of ALB and SLITRK1. WGCNA revealed seven modules correlated with clinical factors, linking preoperative cerebral infarction to the module eigengene (ME) red module and favorable modified Rankin scale scores to the MEblack module. BASP1 and LDHA were significantly upregulated in MEred, whereas CD9 and EMILIN1 were upregulated in MEblack. Our findings shed light on the proteomics of CSF from MMD patients, identifying potential novel biomarkers such as SLITRK1 and markers of preoperative cerebral infarction (BASP1, LDHA) and clinical outcome (CD9, EMILIN1). These markers have potential as new diagnostic and therapeutic targets for MMD.