Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
Key laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
Environ Mol Mutagen. 2022 Jan;63(1):18-28. doi: 10.1002/em.22469. Epub 2021 Dec 28.
Diesel engine exhaust (DEE) is classified as a Group 1 human carcinogen. Using a targeted proteomics approach, we aimed to identify proteins associated with DEE and characterize these markers to understand the mechanisms of DEE-induced carcinogenicity. In this cross-sectional molecular epidemiology study, we measured elemental carbon (EC) using a personal air monitor and quantified 1317 targeted proteins in the serum using the SOMAScan assay (SOMALogic) among 19 diesel exposed factory workers and 19 unexposed controls. We used linear regressions to identify proteins associated with DEE and examined their exposure-response relationship across levels of EC using linear trend tests. We further examined pathway enrichment of DEE-related proteins using MetaCore. Occupational exposure to DEE was associated with altered levels of 22 serum proteins (permutation p < .01). Of these, 13 proteins (CXCL11, HAPLN1, FLT4, CD40LG, PES1, IGHE.IGK..IGL, TNFSF9, PGD, NAGK, CCL25, CCL4L1, PDXK, and PLA2G1B) showed an exposure-response relationship with EC (p trend < .01), with serum levels of all but PLA2G1B declining with increasing air levels of EC. For instance, C-X-C Motif Chemokine Ligand 11 (CXCL11) showed the most significant association with DEE (β = -0.25; permutation p = .00004), where mean serum levels were 4121.1, 2356.7, and 2298.8 relative fluorescent units among the unexposed, lower exposed (median, range : 56.9, 40.2-62.1 μg/m EC), and higher exposed (median, range of EC: 72.9, 66.9-107.7 μg/m EC) groups, respectively (p trend = .0005). Pathway analysis suggested that these proteins are enriched in pathways related to inflammation and immune regulation. Our study suggests that DEE exposure is associated with altered serum proteins, which play a role in inflammation and immune regulation.
柴油机废气（DEE）被归类为人类致癌物质第 1 组。本研究采用靶向蛋白质组学方法，旨在鉴定与 DEE 相关的蛋白质，并对这些标志物进行特征描述，以了解 DEE 致癌作用的机制。在这项横断面分子流行病学研究中，我们使用个人空气监测器测量元素碳（EC），并使用 SOMAScan 测定法（SOMALogic）在 19 名接触柴油机的工厂工人和 19 名未接触的对照者的血清中定量测定了 1317 种靶向蛋白质。我们使用线性回归来鉴定与 DEE 相关的蛋白质，并使用线性趋势检验检查它们在 EC 水平上的暴露-反应关系。我们还使用 MetaCore 检查了与 DEE 相关的蛋白质的途径富集情况。职业性 DEE 暴露与 22 种血清蛋白水平改变有关（置换检验 p < 0.01）。其中，13 种蛋白质（CXCL11、HAPLN1、FLT4、CD40LG、PES1、IGHE.IGK..IGL、TNFSF9、PGD、NAGK、CCL25、CCL4L1、PDXK 和 PLA2G1B）与 EC 呈暴露-反应关系（p 趋势 < 0.01），除 PLA2G1B 外，所有这些蛋白质的血清水平随 EC 空气水平的升高而降低。例如，C-X-C 基序趋化因子配体 11（CXCL11）与 DEE 的关联最显著（β = -0.25；置换检验 p = 0.00004），未暴露组、低暴露组（中位数，范围：56.9，40.2-62.1μg/m EC）和高暴露组（中位数，范围：72.9，66.9-107.7μg/m EC）的血清平均水平分别为 4121.1、2356.7 和 2298.8 相对荧光单位（p 趋势 = 0.0005）。途径分析表明，这些蛋白质富集在与炎症和免疫调节相关的途径中。我们的研究表明，DEE 暴露与改变的血清蛋白质有关，这些蛋白质在炎症和免疫调节中发挥作用。
