Genome-wide gene expression profiling analysis reveals bisphenol A interacts with seven prognosis-related genes to promote the progression of osteosarcoma

Abstract

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 work, we discovered a new method to evaluate the role of BPA in human osteosarcoma (OS). An analysis of genes previously identified as associated with BPA was conducted from the CTD database, and we hypothesized that these genes might be useful as biomarkers, which was proved by protein-protein interactive network. In addition, the KEGG enrichment analysis demonstrated 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 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 osteosarcoma 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.