ArticleBiological trace element research2026
Integrative In Silico and Experimental Analysis Reveals MT1A and HSP70 as Components of a Dual Biomarker Axis for Heavy Metal Exposure.
Article in Biological trace element research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Heavy metal exposure in industrial environments constitutes a significant occupational health risk and can induce systemic oxidative and proteotoxic stress. In this study, in silico toxicogenomics was integrated with population-based validation to identify and confirm candidate biomarkers of heavy metal exposure. Publicly available PBMC microarray data (GSE37567; lead-related exposure model) were analyzed to identify significantly dysregulated genes and enriched biological pathways. Subsequent pathway and protein-protein interaction (PPI) network prioritization, along with toxicogenomics cross-evidence from the Comparative Toxicogenomics Database (CTD), further refined candidate selection. For human validation, PBMC gene expression was assessed by endpoint RT-PCR in a subgroup of four occupationally exposed tannery workers (S1-S4), an additional exposed group from the affected area (n = 10), and (5 + 2) seven controls. Transcriptomic analysis identified 319 significantly dysregulated genes (FDR < 0.05), with notable enrichment of metal homeostasis and cellular stress-response pathways. Metallothionein-related and heat-shock response genes emerged as key network modules, leading to the prioritization of MT1A and HSP70 as a complementary biomarker pair for metal sequestration and proteostasis protection. In the human cohort, MT1A demonstrated consistent induction in exposed individuals (approximately 2.1-2.6-fold, with a maximum of 2.63-fold), while HSP70 expression varied among exposed samples, reflecting heterogeneous exposure and stress-response dynamics. Water analysis from the industrial zone revealed polymetallic contamination, including Pb, Cd, and Cr, supporting the biological plausibility of combined metal-stress responses. Collectively, these findings indicate that MT1A functions as a reliable indicator of metal exposure, whereas HSP70 represents variable stress responses. Together, they offer a complementary framework for assessing stress associated with heavy metal exposure.
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