多队列高维蛋白质组学揭示淋巴癌亚型的早期风险标志物。

Multi-Cohort High-Dimensional Proteomics Reveals Early Risk Markers for Lymphoid Cancer Subtypes.

作者信息

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

出版信息

Res Sq. 2025 Aug 19:rs.3.rs-7400676. doi: 10.21203/rs.3.rs-7400676/v1.

Abstract

This study aims to investigate the early stages of lymphoid malignancy pathogenesis and identify novel pre-diagnostic proteomic markers for lymphoma. Using the SomaScan-7K platform, we analyzed 6,412 unique plasma proteins in a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, comprising 4,565 participants (484 incident lymphoid malignancy cases, median follow-up 9 years). We identified over 500 unique protein-lymphoid malignancy associations. Enriched pathways included 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 revealed concordant nominal significance for 70%-95% of the associations in the UK Biobank (Olink) and ARIC (SomaScan) studies. Time-stratified analyses revealed 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.

摘要

本研究旨在调查淋巴恶性肿瘤发病机制的早期阶段,并确定淋巴瘤新的诊断前蛋白质组学标志物。在欧洲癌症与营养前瞻性调查(EPIC)队列中的一项病例队列研究中,我们使用SomaScan-7K平台分析了6412种独特的血浆蛋白,该队列包括4565名参与者(484例新发淋巴恶性肿瘤病例,中位随访9年)。我们鉴定出500多种独特的蛋白质与淋巴恶性肿瘤的关联。富集的通路包括病毒蛋白相互作用、细胞因子信号传导、B细胞受体信号传导和NF-κB激活,反映了淋巴瘤发病机制中的关键机制。对前20个FDR显著的蛋白质进行跨队列验证,结果显示在英国生物银行(Olink)和动脉粥样硬化风险社区(ARIC)(SomaScan)研究中,70%-95%的关联具有一致的名义显著性。时间分层分析显示,这些蛋白质与淋巴瘤的关联中有一部分在诊断前十年就很明显。这些发现突出了循环蛋白质组学标志物在淋巴恶性肿瘤风险分层、早期诊断和靶向预防策略中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6843/12393504/331256086eea/nihpp-rs7400676v1-f0001.jpg

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