An Integrative Gene Expression Profiling Analysis Indicates Bisphenol A Promotes Osteosarcoma Progression by Interacting With Seven Prognosis-Related Genes

Abstract

With more and more application of the endocrine disruptors (EDCs) in the daily use, there is evidence that EDCs can cause cancer, and they can cause a variety of deleterious effects. It has been known for many years that bisphenol A (BPA), a xenoestrogen found in many consumer products, dysregulates a wide array of signaling pathways in the body. In this study, we employed a novel integrative approach to assess the impact of BPA on human osteosarcoma (OS), leveraging genome-wide gene expression profiling to uncover the molecular interactions and pathways influenced by BPA in this context. In our study, we analyzed genes identified from the Comparative Toxicogenomics Database (CTD) as being associated with BPA. These genes were further examined through protein–protein interaction network analysis to explore their potential interconnectivity and functional roles in the context of human OS. In addition, the KEGG enrichment analysis demonstrated that many cancers, including OS, are closely associated with the BPA. The single sample gene set enrichment analysis algorithm was further used to explore the genes that may play a key role in the OS. An in silico analysis was performed based on gene expression data extracted from TARGET database. On the basis of the BPA-based prognostic prediction model in OS cohort, we discovered that seven BPA-related genes (IHH, ELFN1-AS1, AL161909.1, IGHV4-39, CSAG1, ACTA2, and SSX1) are closely associated with the prognosis of the OS patients. The enrichment pathways analysis reveals that these seven genes are closely associated with the many tumor-related pathways, such as TNFA signaling via NFKB, interferon alpha response, inflammatory response, IL6 JAK STAT3 signaling, and IL2 STAT5 signaling pathways. Additionally, the exposure of 10 μM BPA was found to promote the proliferation ability of OS cells in vitro. Our findings suggest that BPA can promote the proliferation of OS cells. IHH, ELFN1-AS1, AL161909.1, IGHV4-39, CSAG1, ACTA2, and SSX1 are among the most critical targets for BPA to act as a carcinogen.