Unraveling the PFOS-NSCLC axis: integrated network toxicology, machine learning, and causal inference identify EIF4EBP1 as a key molecular hub - PubMed

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PFOS is a persistent environmental pollutant suspected to have carcinogenic potential, particularly linked to non-small cell lung cancer (NSCLC).
The study integrates systems toxicology and multi-omics to explore the role of EIF4EBP1 in connecting PFOS exposure to NSCLC pathogenesis.
Network analysis identified 41 shared targets enriched in PPAR signaling and xenobiotic metabolism, with EIF4EBP1 prioritized as a critical hub gene.
EIF4EBP1 was significantly upregulated in both discovery and validation cohorts, showing subtype-specific prognostic value in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).
High EIF4EBP1 expression correlated with poor survival in LUAD but favorable outcomes in LUSC, and was associated with an adaptive immune-skewed profile.
Mendelian randomization analysis suggested a causal effect of EIF4EBP1 expression on increased LUAD risk, supported by molecular docking showing stable interaction between PFOS and EIF4EBP1.
The study proposes an adverse outcome pathway (AOP) framework where PFOS-mediated translational dysregulation contributes to subtype-specific carcinogenesis.

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