TY - JOUR
T1 - Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes
AU - Kolijn, P. Martijn
AU - Smith-Byrne, Karl
AU - Burk, Vernon
AU - Viallon, Vivian
AU - Lee, Matthew A.
AU - Papier, Keren
AU - Wang, Ziqiao
AU - Langerak, Anton W.
AU - Späth, Florentin
AU - Diepstra, Arjan
AU - Lill, Christina M.
AU - Zamora-Ros, Raul
AU - Macciotta, Alessandra
AU - Aizpurua, Amaia
AU - Tumino, Rosario
AU - Chatterjee, Nilanjan
AU - Travis, Ruth C.
AU - Gunter, Marc J.
AU - Platz, Elizabeth A.
AU - Riboli, Elio
AU - McKay, James
AU - Vermeulen, Roel C.H.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/10/28
Y1 - 2025/10/28
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105020288926
U2 - 10.1038/s41467-025-64534-4
DO - 10.1038/s41467-025-64534-4
M3 - Article
C2 - 41152224
AN - SCOPUS:105020288926
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 9517
ER -