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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月28日

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  • 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

摘要

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.