Comprehensive Blood-based Transcriptomic Signature as a Biomarker for Honeycombing in Pulmonary Fibrosis
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Le résumé fourni par la source
Abstract RATIONALE: Honeycombing (HC) fibrosis is an advanced sign of disease in pulmonary fibrosis (PF), portending poorer prognosis and significantly reduced survival across diverse subtypes of PF. While high-resolution chest CT scans are the gold standard for diagnosing HC, a blood-based transcriptomic biomarker could redefine early diagnostic capabilities and enable stratified patient management. We sought to define blood-based transcriptomic indicators reflecting the presence of HC, assess their diagnostic accuracy, and determine their association with survival outcomes. METHODS: Bulk RNA sequencing was conducted on peripheral blood mononuclear cells from 437 PF patients from the University of Chicago, complemented by 415 patients from the University of California Davis, University of Texas Southwestern, and National Jewish Health for validation. Differential gene expression (DE) analysis compared HC-positive PF patients to non-HC PF patients and healthy donors (n=755 blood, n=578 lung tissue). Transcriptomic profiling was complemented by in-silico cell-type deconvolution to delineate immune cell contributions. RESULTS: We identified 1,317 genes significantly associated with HC in lung tissue (p < 10⁻³, |log₂FC| > 0.5), with 258 genes consistently replicated across multiple models (Fig. 1A). The top DE genes, including TOX2, HECW2, and AFF2, showed congruent expression in blood and lung tissues, positioning them as robust blood-based biomarkers (Fig. 1B). Transcriptome-derived monocyte fractions were disproportionately elevated in the blood of PF patients, suggesting their potential role in fibrotic mechanisms. However, no significant difference in monocyte proportions was observed between HC and non-HC subtypes (Fig. 1C). A blood-based 20-gene HC signature demonstrated predictive capability for HC status (AUC 0.60, 95% CI: 0.55-0.64; χ2=16.66, P=4.5x10⁻5) and was validated in independent cohorts, reinforcing its robustness as a clinical biomarker. Integration of transcriptomic data with clinical outcomes revealed that the 20-gene HC signature strongly correlated with survival in unadjusted and multivariable analyses (HR 1.86, 95% CI: 1.29-2.67; P=1.0x10⁻3)(Fig. 1D). CONCLUSIONS: This study derived and validated a blood-based transcriptomic signature reflecting honeycombing fibrosis, providing an innovative non-invasive diagnostic tool for PF risk stratification. These findings pave the way for targeted molecular diagnostics, personalized therapeutic strategies, and the incorporation of blood transcriptomics into routine clinical evaluations to predict disease trajectory and optimize patient outcomes in PF.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Comprehensive Blood-based Transcriptomic Signature as a Biomarker for Honeycombing in Pulmonary Fibrosis
- Date Crossref
- 01/05/2025
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Chicago Center for Research Informatics pays non établi dans la noticeUniversité ou école supérieure
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University of Michigan Division of Pulmonary and Critical Care Medicine pays non établi dans la noticeUniversité ou école supérieure
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Southwestern Medical Center Department of Medicine pays non établi dans la noticeÉtablissement de santé
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The University of Texas Southwestern Medical Center pays non établi dans la noticeÉtablissement de santé
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National Jewish Health pays non établi dans la noticeÉtablissement de santé
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University of Colorado Denver pays non établi dans la noticeUniversité ou école supérieure
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University of Wisconsin–Madison Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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University of Virginia Division of Pulmonary and Critical Care Medicine pays non établi dans la noticeUniversité ou école supérieure
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Hospital Universitario Nuestra Señora de Candelaria pays non établi dans la noticeÉtablissement de santé
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University of California Internal Medicine pays non établi dans la noticeUniversité ou école supérieure
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Pulmonary and Critical Care pays non établi dans la noticeInstitution
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Research Unit pays non établi dans la noticeStructure de recherche
Center for Research Informatics — University of Chicago, Division of Pulmonary and Critical Care Medicine — University of Michigan et Department of Medicine — Southwestern Medical Center, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.