Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes
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.
Authors
- Christina M. Lill (ORCID: https://orcid.org/0000-0002-2805-1307)
- James McKay
- Amaia Aizpurua
- Alessandra Macciotta (ORCID: https://orcid.org/0000-0002-0287-7979)
- Nilanjan Chatterjee (ORCID: https://orcid.org/0000-0002-9060-008X)
- Elizabeth A. Platz (ORCID: https://orcid.org/0000-0003-3676-8954)
- Matthew A. Lee (ORCID: https://orcid.org/0000-0001-6262-3447)
- Roel C.H. Vermeulen (ORCID: https://orcid.org/0000-0003-4082-8163)
- Ziqiao Wang (ORCID: https://orcid.org/0000-0003-3383-8670)
- Rosario Tumino (ORCID: https://orcid.org/0000-0003-2666-414X)
- Karl Smith-Byrne (ORCID: https://orcid.org/0000-0002-1932-7463)
- Florentin Späth (ORCID: https://orcid.org/0000-0002-0711-0830)
- P. Martijn Kolijn (ORCID: https://orcid.org/0000-0002-2139-637X)
- Elio Ríboli (ORCID: https://orcid.org/0000-0001-6795-6080)
- Marc J. Gunter (ORCID: https://orcid.org/0000-0001-5472-6761)
- Anton W. Langerak (ORCID: https://orcid.org/0000-0002-2078-3220)
- Arjan Diepstra (ORCID: https://orcid.org/0000-0001-9239-1050)
- Keren Papier (ORCID: https://orcid.org/0000-0002-4102-6835)
- Vivian Viallon
- Ruth C. Travis
- Vernon A. Burk
Institutions
- University Medical Center Groningen (NL)
- Johns Hopkins University (US)
- University of Groningen (NL)
- Utrecht University (NL)
- University of Münster (DE)
- Basque Government (ES)
- Erasmus MC (NL)
- University Medical Center Utrecht (NL)
- University of Bristol (GB)
- University of Oxford (GB)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Biogipuzkoa Health Research Institute (ES)
- Institut Català d'Oncologia (ES)
- Italian Association for Cancer Research (IT)
- Department of Public Health (US)
- Centre international de recherche sur le cancer (FR)
- Imperial College London (GB)
- Umeå University (SE)
- Erasmus University Rotterdam (NL)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-28
- DOI
- https://doi.org/10.1038/s41467-025-64534-4
- Primary Topic
- Advanced Proteomics Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Health and Human Services
- World Health Organization
- Compagnia di San Paolo
- Cancer Research UK
- National Institute for Health and Care Research
- Imperial College London
- European Commission
- ZonMw
- Ministero della Salute
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health
- Centers for Disease Control and Prevention
- Medical Research Council
- World Cancer Research Fund
- Instituto de Salud Carlos III
- Rijksinstituut voor Volksgezondheid en Milieu
- School of Public Health, Imperial College London
- National Heart, Lung, and Blood Institute
- National Cancer Institute