Exploring the impact of estrogenic endocrine disruptors on cervical cancer progression: A transcriptome analysis and prognostic model development

Abstract

Cervical cancer is the fourth most common cancer among women globally. The detrimental health effects of estrogenic endocrine disruptors (EED), such as bisphenol A (BPA) and phthalates, are recognized, but their role in cervical cancer progression remains unclear. To investigate this, a transcriptome analysis using bioinformatics was conducted. The Comparative Toxicogenomics Database (CTD) identified estrogen-responsive genes (ERGs) associated with EED. Cervical cancer expression and clinical data were sourced from The Cancer Genome Atlas (TCGA). The limma package identified differentially expressed ERGs (DERGs), which were further analyzed for molecular mechanisms through enrichment analysis. LASSO regression developed a prognostic risk score model, and COX analysis identified prognostic biomarkers. ssGSEA assessed immune tumor infiltration, and Autodock performed molecular docking. A total of 217 DERGs were linked to endocrine resistance, estrogen signaling, and the cell cycle. The prognostic risk score and nomogram based on DERGs were highly predictive of cervical cancer prognosis and could serve as independent risk factors. The risk score influenced the tumor immune microenvironment by affecting immune cell presence. SCARA3 and FASN emerged as independent prognostic factors, with molecular docking confirming strong binding between EED and FASN. DERGs can aid in creating a reliable prognostic model and predicting overall survival in cervical cancer patients, offering new insights into the impact of EED on cancer progression and highlighting environmental factors related to cancer risks and development.