UK Centre for Ecology and Hydrology, Wallingford, UK.
United Kingdom Department for Environment, Food & Rural Affairs, London, UK.
Environ Toxicol Chem. 2022 Sep;41(9):2124-2138. doi: 10.1002/etc.5402. Epub 2022 Aug 3.
Gene expression-based biomarkers are regularly proposed as rapid, sensitive, and mechanistically informative tools to identify whether soil invertebrates experience adverse effects due to chemical exposure. However, before biomarkers could be deployed within diagnostic studies, systematic evidence of the robustness of such biomarkers to detect effects is needed. In our study, we present an approach for conducting a meta-analysis of the robustness of gene expression-based biomarkers in soil invertebrates. The approach was developed and trialed for two measurements of gene expression commonly proposed as biomarkers in soil ecotoxicology: earthworm metallothionein (MT) gene expression for metals and earthworm heat shock protein 70 (HSP70) gene expression for organic chemicals. We collected 294 unique gene expression data points from the literature and used linear mixed-effect models to assess concentration, exposure duration, and species effects on the quantified response. The meta-analysis showed that the expression of earthworm MT was strongly metal concentration dependent, stable over time and species independent. The metal concentration-dependent response was strongest for cadmium, indicating that this gene is a suitable biomarker for this metal. For copper, no clear concentration-dependent response of MT gene expression in earthworms was found, indicating MT is not a reliable biomarker for this metal. For HSP70, overall marginal up-regulation and lack of a concentration-dependent response indicated that this gene is not suitable as a biomarker for organic pollutant effects in earthworms. The present study demonstrates how meta-analysis can be used to assess the status of biomarkers. We encourage colleagues to apply this open-access approach to other biomarkers, as such quantitative assessment is a prerequisite to ensuring that the suitability and limitations of proposed biomarkers are known and stated. Environ Toxicol Chem 2022;41:2124-2138. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
基于基因表达的生物标志物经常被提议作为快速、敏感和具有机制信息的工具，以识别土壤无脊椎动物是否因化学暴露而遭受不良影响。然而，在将生物标志物应用于诊断研究之前，需要有系统的证据证明这些生物标志物检测效应的稳健性。在我们的研究中，我们提出了一种用于分析土壤无脊椎动物中基于基因表达的生物标志物稳健性的荟萃分析方法。该方法是为两种通常被提议作为土壤生态毒理学中生物标志物的基因表达测量而开发和试用的：金属的蚯蚓金属硫蛋白（MT）基因表达和有机化学品的蚯蚓热休克蛋白 70（HSP70）基因表达。我们从文献中收集了 294 个独特的基因表达数据点，并使用线性混合效应模型来评估浓度、暴露时间和物种对量化响应的影响。荟萃分析表明，蚯蚓 MT 的表达强烈依赖于金属浓度，在时间和物种上稳定。镉的金属浓度依赖性反应最强，表明该基因是该金属的合适生物标志物。对于铜，未发现蚯蚓 MT 基因表达对金属浓度的明显依赖性反应，表明 MT 不是该金属的可靠生物标志物。对于 HSP70，总体上调和缺乏浓度依赖性反应表明该基因不适合作为蚯蚓中有机污染物效应的生物标志物。本研究展示了荟萃分析如何用于评估生物标志物的状态。我们鼓励同事将这种开放获取的方法应用于其他生物标志物，因为这种定量评估是确保已知并阐明所提议生物标志物的适用性和局限性的前提。环境毒理学与化学 2022；41：2124-2138。©2022 作者。环境毒理学与化学由 Wiley 期刊公司代表 SETAC 出版。
