Yulin Hospital of the First Affiliated Hospital of Xi'an Jiaotong University, China.
Department of Reproductive Medicine, The First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117025. doi: 10.1016/j.ecoenv.2024.117025. Epub 2024 Sep 19.
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.
宫颈癌是全球女性中第四常见的癌症。人们已经认识到雌激素内分泌干扰物（EED），如双酚 A（BPA）和邻苯二甲酸酯，对健康的有害影响，但它们在宫颈癌进展中的作用仍不清楚。为了研究这一点，我们使用生物信息学进行了转录组分析。比较毒理学基因组学数据库（CTD）确定了与 EED 相关的雌激素反应基因（ERGs）。从癌症基因组图谱（TCGA）获取宫颈癌表达和临床数据。limma 包确定了差异表达的 ERGs（DERGs），并通过富集分析进一步分析其分子机制。LASSO 回归开发了预后风险评分模型，COX 分析确定了预后生物标志物。ssGSEA 评估了肿瘤免疫浸润，Autodock 进行了分子对接。总共 217 个 DERGs 与内分泌抵抗、雌激素信号和细胞周期有关。基于 DERGs 的预后风险评分和列线图对宫颈癌的预后具有高度预测性，可以作为独立的危险因素。风险评分通过影响免疫细胞的存在来影响肿瘤免疫微环境。SCARA3 和 FASN 成为独立的预后因素，分子对接证实了 EED 与 FASN 之间的强结合。DERGs 可以帮助创建可靠的预后模型并预测宫颈癌患者的总生存率，为 EED 对癌症进展的影响提供新的见解，并强调与癌症风险和发展相关的环境因素。
