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Exploring the prognostic implications of PET microplastic degradation products in colorectal cancer: insights from an integrated computational analysis on glucocorticoid pathway–mediated mechanisms
Summary
Researchers used network toxicology, machine learning, and molecular docking to investigate how PET degradation products—ethylene glycol and terephthalic acid—affect colorectal cancer prognosis through the glucocorticoid signaling pathway. The analysis identified 43 shared target genes, suggesting that PET breakdown products may worsen colorectal cancer outcomes by dysregulating glucocorticoid-mediated anti-inflammatory and cell survival signals.
Microplastics (MPs) and their degradation products pose growing environmental and health risks. This study investigates how polyethylene terephthalate (PET)-derived degradation products, ethylene glycol (EG) and terephthalic acid (TPA), influence colorectal cancer (CRC) prognosis. Integrating network toxicology, machine learning (ML), and molecular docking, we identified 43 genes linking EG/TPA exposure to CRC pathogenesis. Functional enrichment analysis revealed their involvement in TNF/IL-17 signaling and glucocorticoid (GC)-mediated metabolic pathways, synergistically promoting chronic inflammation and immune suppression. Prognostic ML models prioritized SPP1, TJP1, and DDIT3 as hub genes significantly correlated with poor survival outcomes. Molecular docking confirmed EG's stable binding to these targets, suggesting mechanisms involving cytoskeletal remodeling, tight junction disruption, and endoplasmic reticulum stress. Notably, GC pathway activation emerged as a critical driver of CRC progression, facilitating tumor immune evasion and therapy resistance. Our findings highlight the prognostic relevance of PET-derived MPs via GC signaling dysregulation, providing mechanistic insights into how environmental pollutants exacerbate cancer risks. This study advances strategies for refining MPs toxicity assessments and developing targeted interventions to mitigate CRC progression linked to MPs exposure.