Discovery of novel biomarkers by microarray analysis of peripheral blood mononuclear cell gene expression in benzene-exposed workers.
Discovery of novel biomarkers by microarray analysis of peripheral blood mononuclear cell gene expression in benzene-exposed workers.
复制标题
通过微阵列分析在暴露于苯的工人中发现新型生物标志物。
DOI：
10.1289/ehp.7635
复制
发表时间：
2005-06
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
--
作者：
苯是一种工业化学品，也是汽油的组成部分，是白血病的一个确定原因。为了更好地了解苯带来的风险，我们研究了苯暴露对鞋厂工人外周血单核细胞（PBMC）基因表达的影响，这些工人具有良好的职业暴露特征，使用微阵列和实时聚合酶链反应（PCR）。PBMC RNA在现场稳定化，并使用全面的人阵列U133 A/B Affyssin基因芯片组进行分析。对6个暴露-对照对进行匹配分析。稳健的多阵列分析和使用配对t统计的基因排序的组合，沿着引导以控制5%的家族错误率，用于在全局分析中鉴定差异表达的基因。这导致了一组29个已知的基因被鉴定出极有可能差异表达。我们还对508个细胞因子探针集的较小子集重复了这些分析，发现暴露受试者和对照受试者之间19个已知细胞因子基因的表达存在显著差异。通过实时PCR选择了6个基因进行确认，其中CXCL 16，ZNF 331，JUN和PF 4受苯暴露的影响最显著，这一发现在来自28名受试者的更大数据集中得到了证实。改变的表达不是由PBMC组分的组成变化引起的。因此，微阵列分析沿着实时PCR确认揭示了CXCL 16、ZNF 331、JUN和PF 4的表达改变是苯暴露的潜在生物标志物。
Benzene is an industrial chemical and component of gasoline that is an established cause of leukemia. To better understand the risk benzene poses, we examined the effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression in a population of shoe-factory workers with well-characterized occupational exposures using microarrays and real-time polymerase chain reaction (PCR). PBMC RNA was stabilized in the field and analyzed using a comprehensive human array, the U133A/B Affymetrix GeneChip set. A matched analysis of six exposed–control pairs was performed. A combination of robust multiarray analysis and ordering of genes using paired t-statistics, along with bootstrapping to control for a 5% familywise error rate, was used to identify differentially expressed genes in a global analysis. This resulted in a set of 29 known genes being identified that were highly likely to be differentially expressed. We also repeated these analyses on a smaller subset of 508 cytokine probe sets and found that the expression of 19 known cytokine genes was significantly different between the exposed and the control subjects. Six genes were selected for confirmation by real-time PCR, and of these, CXCL16, ZNF331, JUN, and PF4 were the most significantly affected by benzene exposure, a finding that was confirmed in a larger data set from 28 subjects. The altered expression was not caused by changes in the makeup of the PBMC fraction. Thus, microarray analysis along with real-time PCR confirmation reveals that altered expressions of CXCL16, ZNF331, JUN, and PF4 are potential biomarkers of benzene exposure.