Drizik E, Corbett S, Zheng Y, Vermeulen R, Dai Y, Hu W, Ren D, Duan H, Niu Y, Xu J, Fu W, Meliefste K, Zhou B, Zhang Xiaohui, Yang J, Bassig Bryan, Liu Hanqiao, Ye M, Liu Gang, Jia X, Meng T, Bin P, Zhang J, Silverman D, Spira A, Rothman N, Lenburg M E, Lan Q
Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Bioinformatics Program, Boston University, Boston, MA, USA.
Environ Int. 2020 Apr;137:105506. doi: 10.1016/j.envint.2020.105506. Epub 2020 Feb 7.
Diesel engine exhaust (DEE) exposure causes lung cancer, but the molecular mechanisms by which this occurs are not well understood.
To assess transcriptomic alterations in nasal epithelium of DEE-exposed factory workers to better understand the cellular and molecular effects of DEE.
Nasal epithelial brushings were obtained from 41 diesel engine factory workers exposed to relatively high levels of DEE (17.2-105.4 μg/m), and 38 unexposed workers from factories without DEE exposure. mRNA was profiled for gene expression using Affymetrix microarrays. Linear modeling was used to identify differentially expressed genes associated with DEE exposure and interaction effects with current smoking status. Pathway enrichment among differentially expressed genes was assessed using EnrichR. Gene Set Enrichment Analysis (GSEA) was used to compare gene expression patterns between datasets.
225 genes had expression associated with DEE exposure after adjusting for smoking status (FDR q < 0.25) and were enriched for genes in pathways related to oxidative stress response, cell cycle pathways such as MAPK/ERK, protein modification, and transmembrane transport. Genes up-regulated in DEE-exposed individuals were enriched among the genes most up-regulated by cigarette smoking in a previously reported bronchial airway smoking dataset. We also found that the DEE signature was enriched among the genes most altered in two previous studies of the effects of acute DEE on PBMC gene expression. An exposure-response relationship was demonstrated between air levels of elemental carbon and the first principal component of the DEE signature.
A gene expression signature was identified for workers occupationally exposed to DEE that was altered in an exposure-dependent manner and had some overlap with the effects of smoking and the effects of acute DEE exposure. This is the first study of gene expression in nasal epithelial cells of workers heavily exposed to DEE and provides new insights into the molecular alterations that occur with DEE exposure.
接触柴油机尾气（DEE）会导致肺癌，但其发生的分子机制尚不清楚。
评估接触DEE的工厂工人鼻上皮的转录组变化，以更好地了解DEE的细胞和分子效应。
从41名接触相对高水平DEE（17.2 - 105.4μg/m）的柴油机工厂工人以及38名未接触DEE的非柴油机工厂工人中获取鼻上皮刷片。使用Affymetrix微阵列对mRNA进行基因表达谱分析。采用线性模型识别与DEE暴露相关的差异表达基因以及与当前吸烟状态的交互作用。使用EnrichR评估差异表达基因中的通路富集情况。基因集富集分析（GSEA）用于比较数据集之间的基因表达模式。
在调整吸烟状态后，有225个基因的表达与DEE暴露相关（FDR q < 0.25），这些基因在与氧化应激反应、细胞周期途径（如MAPK/ERK）、蛋白质修饰和跨膜运输相关的通路中富集。在接触DEE的个体中上调的基因，在先前报道的支气管气道吸烟数据集中，富集于吸烟上调程度最高的基因之中。我们还发现，在之前两项关于急性DEE对PBMC基因表达影响的研究中，DEE特征在变化最大的基因中富集。元素碳的空气水平与DEE特征的第一主成分之间呈现出暴露 - 反应关系。
确定了职业接触DEE的工人的基因表达特征，其以暴露依赖的方式发生改变，并且与吸烟效应和急性DEE暴露效应存在一些重叠。这是首次对大量接触DEE的工人鼻上皮细胞中的基因表达进行研究，为DEE暴露时发生的分子改变提供了新的见解。
