Examination of the Association Between Bisphenol-Related Genes and Lung Cancer

Abstract

In recent years, the release of substantial amounts of synthetic endocrine-disrupting chemicals (EDCs) into the environment has posed significant threats to human health. Among these EDCs, bisphenol A (BPA) and its substitutes, such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), are widely used and have been implicated in disrupting various biological processes. This research aimed to evaluate the potential link between bisphenol-related gene expression and lung cancer prognosis. Using the Comparative Toxicogenomics Database (CTD), we identified genes involved in bisphenol metabolism and their significant associations with key oncogenes and hormone-disrupting pathways, including INS, ESR1, ESR2, AR, MAPK1, MAPK3, PPARG, and CYP19A1. Our Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicate that bisphenol-related genes may be associated with a variety of cancers, particularly lung cancer. To develop a risk model, we employed Cox regression and LASSO regression analyses, constructing a prognostic prediction model for lung cancer based on bisphenol-related gene expression (BBPPM). This model demonstrated prognostic significance, with lung cancer patients categorized into high-risk and low-risk groups, revealing significant differences in survival rates and highlighting the model’s accuracy in predicting lung cancer outcomes. In addition to bioinformatics analyses, experimental studies were conducted to evaluate the effect of BPA on lung cancer cell behavior. BPA exposure significantly promoted the proliferation of A549 lung cancer cells, as assessed by the CCK-8 assay, and increased the clonogenic potential of the cells in a colony formation assay.