Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes
Nature Communications, 2025
Kolijn P., Smith-Byrne K., Burk V., Viallon V., Lee M., Papier K., Wang Z., Langerak A., Späth F., Diepstra A., Lill C., Zamora-Ros R., Macciotta A., Aizpurua A., Tumino R., Chatterjee N., Travis R., Gunter M., Platz E., Riboli E., McKay J., Vermeulen R.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Oncology | Patient Stratification | Plasma |  Olink Explore 3072/384 |
Abstract
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.