Linking bisphenol a exposure to pancreatic cancer: Evidence from population epidemiology, multi-omics screening, and cellular validation.

Metabolomics insights into the association between organochlorine pesticides, synthetic pyrethroids exposure and thyroid cancer risk.

BACKGROUND The association between organochlorine pesticides (OCPs)/synthetic pyrethroids (SPs) and thyroid cancer (TC) remains poorly understood, with metabolic mechanisms unexplored. METHODS We conducted a 1:1 age- and sex-matched case-control study (n = 668). Serum levels of 27 target analytes (19 OCPs and 8 SPs) were quantified; subsequent analyses were restricted to 13 compounds (10 OCPs and 3 SPs) with detection frequencies ≥85%. Eight machine learning (ML) algorithms with Shapley Additive Explanations (SHAP) were used to identify key pollutants in the 334 case-control pairs. Untargeted metabolomics was performed in a subset of 50 age- and sex-matched case-control pairs. Mixture effects were assessed by Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression. Furthermore, the Latent Unknown Clustering Integrating Multi-Omics Data (LUCID) model was employed to integrate exposure and metabolic data, enabling the identification of TC patient subgroups and the exploration of underlying metabolic mechanisms. RESULTS Participants (mean age 45.2 years, 82.3% female) had serum OCPs at 0.007-0.333 ng/mL and SPs at 0.046-0.095 ng/mL. ML algorithms identified fenpropathrin, β-BHC, cyhalothrin, α-BHC, and p,p'-DDD as the top five contributors to TC. Elevated OCPs/SPs exposure was significantly associated with increased TC risk (WQS: adjusted OR = 1.45, 95%CI = 1.34-2.24, P = 0.019; LUCID: OR = 9.33). Fenpropathrin was the primary contributor (BKMR posterior inclusion probability = 1.00; WQS weight = 67.6%). A total of 45 significant differential metabolites (DMs) were identified (VIP ≥1, P < 0.05, and qualitative level 1). LUCID revealed a distinct TC cluster characterized by upregulated S-sulfo-L-cysteine/adenosine and downregulated 2-hydroxycaprylic acid. CONCLUSION OCPs/SPs mixtures, driven by fenpropathrin, disrupt amino acid/nucleotide metabolism while suppressing organic acid metabolism, representing a potential TC-associated metabolic signature.

BDE47 exposure in lung adenocarcinoma: prognostic biomarkers, immune dysregulation, and mechanistic insights from toxicogenomic and docking studies

How BDE47 exposure may influence lung adenocarcinoma and highlights the need for environmental pollutant monitoring, while also offering potential biomarkers for cancer prognosis and treatment is revealed.

A network toxicology and machine learning approach to uncover the molecular machinery of bisphenol A-induced colorectal cancer

The machine learning-derived 12-gene signature, interpreted as CRC-associated genes overlapping with predicted BPA targets and supported by in silico molecular docking, offers valuable insights into the molecular basis of BPA-associated colorectal carcinogenesis and presents candidate targets for subsequent experimental validation.

Bisphenol A promotes colorectal cancer malignancy through CXCL8 upregulation associated with p38 MAPK activation: A potential link to type 2 diabetes mellitus comorbidity.

BACKGROUND Bisphenol A (BPA) is a common environmental endocrine disruptor linked to type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC), but the exact mechanism connecting BPA exposure to their comorbidity is unclear. METHODS This study integrated network toxicology, single-cell transcriptomic data, molecular simulation, in vitro cell experiments, and patient-derived explant (PDE) models to systematically explore the potential molecular basis underlying the correlation between BPA exposure and T2DM-CRC comorbidity. RESULTS CXCL8 was identified as the sole overlapping gene shared among the 30 BPA-T2DM-CRC common targets, the PPI-derived hub genes, and the DEGs identified in GSE115313. It was upregulated in T2DM-CRC tissues, associated with obesity and T2DM, and showed strong diagnostic performance in CRC (AUC=0.895). Immune analysis indicated an increased proportion of Tregs in CRC samples from patients with T2DM, while CXCL8 expression correlated positively with M1 macrophage and activated mast cell infiltration. Single-cell transcriptomic data analysis of GSE188711 showed that CXCL8 expression varied along the inferred pseudotime trajectory and appeared enriched in the annotated B-cell population. Molecular simulations showed moderate binding between BPA and CXCL8 (binding energy: -5.7 kcal/mol). BPA treatment boosted CRC cell proliferation, migration, and invasion, while CXCL8 knockdown reduced these activities. The malignant effects of BPA were significantly reduced when CXCL8 was knocked down. Mechanistically, TEAD4 was identified as a potential upstream transcriptional regulator of CXCL8, while increased CXCL8 expression was accompanied by enhanced p38 MAPK pathway activation. CONCLUSIONS BPA-induced CXCL8 upregulation is associated with CRC malignant progression and enhanced p38 MAPK signaling. TEAD4 may function as an upstream transcriptional regulator of CXCL8, although its direct regulation by BPA remains unclear. Given the clinical correlation between CXCL8 upregulation and T2DM status, this pathway may represent a potential mechanistic link contributing to the frequently observed T2DM-CRC comorbidity.

Integrative Multi-Omics Analysis Identifies Key Molecular Targets Linking Bisphenol A Exposure to Gestational Diabetes Mellitus.

Bisphenol A and ovarian cancer: emerging evidence and potential biological mechanisms

Overall, evidence linking BPA exposure to ovarian-cancer-related outcomes remains limited, and current findings do not establish that BPA causes OC or worsens patient prognosis in humans.