探索雌激素内分泌干扰物对宫颈癌进展的影响:转录组分析和预后模型的建立

IF 6.2 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Ecotoxicology and Environmental Safety Pub Date : 2024-09-19 DOI:10.1016/j.ecoenv.2024.117025
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引用次数: 0

摘要

宫颈癌是全球妇女第四大常见癌症。双酚 A(BPA)和邻苯二甲酸盐等雌激素内分泌干扰物(EED)对健康的有害影响已得到公认,但它们在宫颈癌进展中的作用仍不清楚。为了研究这个问题,我们利用生物信息学进行了转录组分析。比较毒物基因组学数据库(CTD)确定了与 EED 相关的雌激素反应基因(ERGs)。宫颈癌表达和临床数据来自癌症基因组图谱(TCGA)。limma软件包确定了差异表达的ERGs(DERGs),并通过富集分析进一步分析了其分子机制。ssGSEA评估免疫肿瘤浸润,Autodock进行分子对接。共有217个DERGs与内分泌抗性、雌激素信号转导和细胞周期有关。基于 DERGs 的预后风险评分和提名图对宫颈癌的预后有很高的预测性,可作为独立的风险因素。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有助于建立可靠的预后模型和预测宫颈癌患者的总生存期,为EED对癌症进展的影响提供了新的见解,并突出了与癌症风险和发展相关的环境因素。
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Exploring the impact of estrogenic endocrine disruptors on cervical cancer progression: A transcriptome analysis and prognostic model development

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.

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来源期刊
CiteScore
12.10
自引率
5.90%
发文量
1234
审稿时长
88 days
期刊介绍: Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.
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