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Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes
Division of Environmental Epidemiology and Veterinary Public Health, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands; Julius Global Health, the Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Netherlands; Department of Immunology, Erasmus MC, Rotterdam, Netherlands.
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
International Agency for Research on Cancer (IARC) - World Health Organization, Lyon, France.
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2025 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 16, no 1, article id 9517Article in journal (Refereed) Published
Abstract [en]

This study aims to investigate the early stages of lymphoid malignancy pathogenesis and identify pre-diagnostic proteomic markers for lymphoma. Using the SomaScan-7K platform, we analyze 6412 unique plasma proteins in a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, comprising 4565 participants (484 incident lymphoid malignancy cases, median follow-up 9 years). We identify over 500 unique protein-lymphoid malignancy associations. Enriched pathways include viral protein interactions, cytokine signaling, B-cell receptor signaling, and NF-κB activation, reflecting key mechanisms in lymphoma pathogenesis. Cross-cohort validation of the top 20 FDR-significant proteins reveals concordant nominal significance for 70%-95% of the associations in the UK Biobank (Olink) and ARIC (SomaScan) studies. Time-stratified analyses reveals that a subset of these protein-lymphoma associations is evident over a decade before diagnosis. These findings highlight the potential of circulating proteomic markers in risk stratification, early diagnosis, and targeted prevention strategies for lymphoid malignancies.

Place, publisher, year, edition, pages
Springer Nature, 2025. Vol. 16, no 1, article id 9517
National Category
Cancer and Oncology
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URN: urn:nbn:se:umu:diva-246832DOI: 10.1038/s41467-025-64534-4ISI: 001604755900007PubMedID: 41152224Scopus ID: 2-s2.0-105020288926OAI: oai:DiVA.org:umu-246832DiVA, id: diva2:2016026
Available from: 2025-11-24 Created: 2025-11-24 Last updated: 2025-11-24Bibliographically approved

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Späth, Florentin

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