Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes

P Martijn Kolijn; Karl Smith-Byrne; Vernon Burk; Vivian Viallon; Matthew A Lee; Keren Papier; Ziqiao Wang; Anton W Langerak; Florentin Späth; Arjan Diepstra; Christina M Lill; Raul Zamora-Ros; Alessandra Macciotta; Amaia Aizpurua; Rosario Tumino; Nilanjan Chatterjee; Ruth C Travis; Marc J Gunter; Elizabeth A Platz; Elio Riboli; James McKay; Roel C H Vermeulen

doi:10.1038/s41467-025-64534-4

Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes

P Martijn Kolijn, Karl Smith-Byrne, Vernon Burk, Vivian Viallon, Matthew A Lee, Keren Papier, Ziqiao Wang, Anton W Langerak, Florentin Späth, Arjan Diepstra, Christina M Lill, Raul Zamora-Ros, Alessandra Macciotta, Amaia Aizpurua, Rosario Tumino, Nilanjan Chatterjee, Ruth C Travis, Marc J Gunter, Elizabeth A Platz, Elio RiboliJames McKay, Roel C H Vermeulen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	9517
Number of pages	14
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-64534-4
Publication status	Published - 28 Oct 2025

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© The Author(s) 2025.

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Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypesFinal published version, 1.27 MBLicence: CC BY-NC-ND

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Kolijn, P. M., Smith-Byrne, K., Burk, V., Viallon, V., Lee, M. A., Papier, K., Wang, Z., Langerak, A. W., Späth, F., Diepstra, A., Lill, C. M., Zamora-Ros, R., Macciotta, A., Aizpurua, A., Tumino, R., Chatterjee, N., Travis, R. C., Gunter, M. J., Platz, E. A., ... Vermeulen, R. C. H. (2025). Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes. Nature Communications, 16(1), Article 9517. https://doi.org/10.1038/s41467-025-64534-4

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title = "Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes",

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.",

author = "Kolijn, \{P Martijn\} and Karl Smith-Byrne and Vernon Burk and Vivian Viallon and Lee, \{Matthew A\} and Keren Papier and Ziqiao Wang and Langerak, \{Anton W\} and Florentin Sp{\"a}th and Arjan Diepstra and Lill, \{Christina M\} and Raul Zamora-Ros and Alessandra Macciotta and Amaia Aizpurua and Rosario Tumino and Nilanjan Chatterjee and Travis, \{Ruth C\} and Gunter, \{Marc J\} and Platz, \{Elizabeth A\} and Elio Riboli and James McKay and Vermeulen, \{Roel C H\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = oct,

day = "28",

doi = "10.1038/s41467-025-64534-4",

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Kolijn, PM, Smith-Byrne, K, Burk, V, Viallon, V, Lee, MA, Papier, K, Wang, Z, Langerak, AW, Späth, F, Diepstra, A, Lill, CM, Zamora-Ros, R, Macciotta, A, Aizpurua, A, Tumino, R, Chatterjee, N, Travis, RC, Gunter, MJ, Platz, EA, Riboli, E, McKay, J & Vermeulen, RCH 2025, 'Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes', Nature Communications, vol. 16, no. 1, 9517. https://doi.org/10.1038/s41467-025-64534-4

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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

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.

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DO - 10.1038/s41467-025-64534-4

M3 - Article

C2 - 40894013

SN - 2041-1723

VL - 16

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 9517

ER -

Multi-cohort high-dimensional proteomics reveals early risk markers for lymphoid cancer subtypes

Abstract

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