Integrated DNA methylation analysis of peripheral blood from asbestos exposed populations and patients with malignant mesothelioma reveals novel methylation driver genes of diagnostic and prognostic relevance

IF 7.6 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Environmental Pollution Pub Date : 2024-09-13 DOI:10.1016/j.envpol.2024.124928

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Abstract

Effective biomarkers are paramount importance for the early detection and prognosis prediction of malignant mesothelioma (MM) which mainly caused by asbestos exposure, and DNA methylation has been demonstrated to be a potentially powerful diagnostic tool. To elucidate the relationship between asbestos exposure and alterations in DNA methylation patterns, as well as the potential diagnostic and prognostic value of differentially methylated regions and CpG sites (DMRs/DMCs) in the progression of MM. The current study employed reduced representation bisulﬁte sequencing (RRBS) to examine the genome-wide DNA methylation profiles in the peripheral blood of individuals exposed to asbestos and those diagnosed with MM, in comparison to the controls, and DMRs/DMCs were subsequently validated by targeted bisulfite sequencing (TBS). Our results suggested that there were 12 DMRs/DMCs exhibiting a consistent change trend of DNA methylation in both RRBS and TBS results. Significant correlations were observed between DNA methylation levels of DMRs/DMCs and the duration of occupational asbestos exposure. The evaluation of the receiver operating characteristic (ROC) curve suggested that the DNA methylation status of FHIT, CCR12P and CDH15 may serve as diagnosis indicator in distinguishing MM patients from healthy controls and those exposed to asbestos. Our findings offer a foundation for the role of DNA methylation in the development of MM induced by asbestos exposure. The potential significance of FHIT, CCR12P and CDH15 DNA methylation alterations in the pathogenesis and advancement of MM disease suggests their potential as diagnostic and prognostic biomarkers.

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对暴露于石棉的人群和恶性间皮瘤患者的外周血进行 DNA 甲基化综合分析，发现与诊断和预后相关的新型甲基化驱动基因

有效的生物标志物对于主要由石棉暴露引起的恶性间皮瘤（MM）的早期检测和预后预测至关重要，而DNA甲基化已被证明是一种潜在的强大诊断工具。为了阐明石棉暴露与DNA甲基化模式改变之间的关系，以及不同甲基化区域和CpG位点（DMRs/DMCs）在MM进展中的潜在诊断和预后价值。本研究采用还原表征双硫酸测序（RRBS）技术，检测了暴露于石棉的个体和确诊为 MM 的个体外周血中与对照组相比的全基因组 DNA 甲基化图谱，随后通过靶向亚硫酸氢盐测序（TBS）对 DMRs/DMCs 进行了验证。我们的研究结果表明，有 12 个 DMRs/DMCs 在 RRBS 和 TBS 结果中表现出一致的 DNA 甲基化变化趋势。DMRs/DMCs的DNA甲基化水平与职业石棉暴露时间之间存在显著相关性。接受者操作特征曲线（ROC）评估表明，FHIT、CCR12P 和 CDH15 的 DNA 甲基化状态可作为诊断指标，用于区分 MM 患者与健康对照组和暴露于石棉的患者。我们的研究结果为 DNA 甲基化在石棉暴露诱发的 MM 发病中的作用提供了依据。FHIT、CCR12P和CDH15 DNA甲基化改变在MM发病和发展过程中的潜在意义表明，它们具有作为诊断和预后生物标志物的潜力。

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来源期刊

Environmental Pollution 环境科学-环境科学

CiteScore

16.00

自引率

6.70%

发文量

2082

审稿时长

2.9 months

期刊介绍： Environmental Pollution is an international peer-reviewed journal that publishes high-quality research papers and review articles covering all aspects of environmental pollution and its impacts on ecosystems and human health. Subject areas include, but are not limited to: • Sources and occurrences of pollutants that are clearly defined and measured in environmental compartments, food and food-related items, and human bodies; • Interlinks between contaminant exposure and biological, ecological, and human health effects, including those of climate change; • Contaminants of emerging concerns (including but not limited to antibiotic resistant microorganisms or genes, microplastics/nanoplastics, electronic wastes, light, and noise) and/or their biological, ecological, or human health effects; • Laboratory and field studies on the remediation/mitigation of environmental pollution via new techniques and with clear links to biological, ecological, or human health effects; • Modeling of pollution processes, patterns, or trends that is of clear environmental and/or human health interest; • New techniques that measure and examine environmental occurrences, transport, behavior, and effects of pollutants within the environment or the laboratory, provided that they can be clearly used to address problems within regional or global environmental compartments.