Per- and Polyfluoroalkyl Substances and Papillary Thyroid Carcinoma: An Integrative Study of Bioinformatics,...

Per- and polyfluoroalkyl substances (PFAS) have been associated with thyroid dysfunction, but their relationship with papillary thyroid carcinoma (PTC) and relevant molecular processes remains unclear. We integrated bioinformatics analyses, a hospital-based case-control study, and in vitro experiments to investigate associations between PFAS exposure and PTC and to explore potentially relevant post-transcriptional RNA regulatory processes. Transcriptomic data, PFAS-associated genes, and m⁷G-associated genes were integrated to identify candidate genes. Among 24 overlapping candidates, 21 remained differentially expressed between PTC and normal thyroid tissues after false discovery rate correction, and EIF4E, NCBP1, and AGO2 were identified as candidate hub genes. The case-control study included 60 patients with newly diagnosed PTC and 60 controls. Serum concentrations of 17 PFAS were measured, and individual and mixture associations with PTC status were evaluated using logistic regression, weighted quantile sum regression, quantile g-computation, and Bayesian kernel machine regression. Higher concentrations of several PFAS were associated with lower odds of PTC, although the findings were not fully consistent across analytical models. In vitro, high concentrations of PFOA and PFOS reduced relative thyroid-cell viability, whereas wound-healing responses were variable and did not show a consistent enhancement. PFOA and PFOS exposure was also accompanied by altered EIF4E and NCBP1 mRNA expression, respectively. Overall, these findings support an association between PFAS exposure and PTC and identify m⁷G-associated post-transcriptional regulatory candidates, particularly EIF4E and NCBP1, that may contribute to PFAS-related thyroid cellular responses and warrant further mechanistic investigation.