Li Jianing, Bian Xiaofeng, Zhang Caixia, Chen Yirong, Huang Shijia, Zhao Shuli, Li Yanchuan
Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Central Laboratory of Nanjing Medical University Affiliated Nanjing Hospital, Nanjing, China.
Ecotoxicol Environ Saf. 2025 Feb;291:117831. doi: 10.1016/j.ecoenv.2025.117831. Epub 2025 Feb 16.
Perfluorooctanoic acid (PFOA) exposure has been implicated in various health issues. This study aims to identify common genes associated with PFOA exposure and ovarian cancer, elucidate their biological functions, and explore their prognostic significance.
We identified common genes linked to PFOA exposure and ovarian cancer using the Comparative Toxicogenomics Database. Protein-protein interaction and functional enrichment analyses were performed via Metascape. A PFOA-related risk model was developed using TCGA data and LASSO regression. Survival and expression analyses were conducted, and a prognostic nomogram was created. Tumor immune microenvironment interactions were investigated using ESTIMATE and ssGSEA methods. Molecular docking studies assessed the binding affinities between PFOA and target proteins.
Utilizing the Comparative Toxicogenomics Database, we identified 229 common genes linked to both PFOA exposure and ovarian cancer. A comprehensive protein-protein interaction (PPI) network analysis revealed distinct functional modules. Enrichment analysis indicated significant involvement of these genes in pathways like the PI3K-Akt signaling pathway and focal adhesion. Lasso regression identified seven key prognostic genes (ERBB2, CCNH, PDE2A, CXCL11, TIAM1, SLC9A1, and EPHA2), with survival analysis demonstrating that PFOA-related high risk group exhibited significantly worse overall survival. Expression analysis showed the dysregulation of key prognostic genes in tumor tissues, while immune correlation analysis indicated significant associations with the tumor microenvironment. Molecular docking and molecular dynamics simulations revealed strong binding affinities between PFOA and the PDE2A.
Overall, this research contributes to a deeper understanding of the health risks associated with PFOA exposure and highlights the importance of continued monitoring and regulation of environmental pollutants to safeguard public health.
全氟辛酸(PFOA)暴露与多种健康问题有关。本研究旨在确定与PFOA暴露和卵巢癌相关的常见基因,阐明其生物学功能,并探讨其预后意义。
我们使用比较毒理基因组学数据库确定了与PFOA暴露和卵巢癌相关的常见基因。通过Metascape进行蛋白质-蛋白质相互作用和功能富集分析。利用TCGA数据和LASSO回归建立了PFOA相关风险模型。进行了生存和表达分析,并创建了预后列线图。使用ESTIMATE和ssGSEA方法研究肿瘤免疫微环境相互作用。分子对接研究评估了PFOA与靶蛋白之间的结合亲和力。
利用比较毒理基因组学数据库,我们确定了229个与PFOA暴露和卵巢癌相关的常见基因。全面的蛋白质-蛋白质相互作用(PPI)网络分析揭示了不同的功能模块。富集分析表明这些基因在PI3K-Akt信号通路和粘着斑等途径中显著参与。Lasso回归确定了七个关键预后基因(ERBB2、CCNH、PDE2A、CXCL11、TIAM1、SLC9A1和EPHA2),生存分析表明PFOA相关高风险组的总生存期明显更差。表达分析显示肿瘤组织中关键预后基因失调,而免疫相关性分析表明与肿瘤微环境有显著关联。分子对接和分子动力学模拟揭示了PFOA与PDE2A之间有很强的结合亲和力。
总体而言,本研究有助于更深入地了解与PFOA暴露相关的健康风险,并强调持续监测和监管环境污染物以保障公众健康的重要性。