ArticleEBioMedicine2024
Circulating biomarkers in familial cerebral cavernous malformation.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06983132 (Natural History of Familial Cerebral Cavernous Malformations), which is not on this map. Cited by 14 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Natural History of Familial Cerebral Cavernous Malformations: the CCM_Italia Cohort Study
Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.
- Imaging markers and circulating biomarkers for predicting hemorrhage from cerebral cavernous malformations: A systematic review.Neurosurgical review · 2026Pooled it
- Molecular Pathways and Circulating Biomarkers in Cerebral Cavernous Malformations-A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Human stem cell models in cerebral cavernous malformations.Stem cell research & therapy · 2026Review
- MEKK3 bridges gut-brain communication and cerebral cavernous malformation pathogenesis.Cell death discovery · 2026Review
- Familial Cerebral Cavernous Malformations: Pathophysiology, Genetics, Biomarkers, and Treatment Perspectives.Journal of neurochemistry · 2026Review
- Microbial oncogenesis: the impact of Fusobacterium nucleatum on oral cancer pathways.Medical oncology (Northwood, London, England) · 2025Review
- Familial Cerebral Cavernous Malformations : A Clinical Series and Literature Review.Journal of Korean Neurosurgical Society · 2025Article
- Single-cell sequencing insights into the transcriptional landscape of cerebral cavernous malformations.Angiogenesis · 2025Review
- Persistent Activation of Endothelial Cells is Linked to Thrombosis and Inflammation in Cerebral Cavernous Malformation Disease.bioRxiv : the preprint server for biology · 2025Article
- Review
- Plasma biomarkers in patients with familial cavernous malformation and their first-degree relatives: a cross-sectional study.Scientific reports · 2025Observational
- Natural history of familial cerebral cavernous malformations: the CCM_Italia cohort study.Frontiers in neurology · 2025Article
- Case Report: Single-cell RNA sequencing reveals cellular and molecular mechanisms in newborn cardiac hemangioma formation.Frontiers in cardiovascular medicine · 2025Article
- Recent novelties in research and management of cerebrospinal cavernous malformations.Acta neurochirurgica · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 14 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PDCD10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression.
methodsHere, we have investigated plasma samples derived from n = 71 symptomatic fCCM patients (40 female/31 male) and n = 17 healthy donors (HD) (9 female/8 male) of the Phase 1/2 Treat_CCM trial, using multiplexed protein profiling approaches.
findingsBiomarkers as sCD14 (p = 0.00409), LBP (p = 0.02911), CXCL4 (p = 0.038), ICAM-1 (p = 0.02013), ANG2 (p = 0.026), CCL5 (p = 0.00403), THBS1 (p = 0.0043), CRP (p = 0.0092), and HDL (p = 0.027), were significantly different in fCCM compared to HDs. Of note, sENG (p = 0.011), THBS1 (p = 0.011) and CXCL4 (p = 0.011), were correlated to CCM genotype. sROBO4 (p = 0.014), TM (p = 0.026) and CRP (p = 0.040) were able to predict incident adverse clinical events, such as ICH, FND or seizure. GDF-15, FLT3L, CXCL9, FGF-21 and CDCP1, were identified as predictors of the formation of new MRI-detectable lesions over 2-year follow-up. Furthermore, the functional relevance of ang2, thbs1, robo4 and cdcp1 markers was validated by zebrafish pre-clinical model of fCCM.
interpretationOverall, our study identifies a set of biochemical parameters to predict CCM progression, suggesting biological interpretations and potential therapeutic approaches to CCM disease.
fundingItalian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro (AIRC), ERC, Leducq Transatlantic Network of Excellence, Swedish Research Council.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.