Abstract：
BACKGROUND: Breast cancer represents one of the leading causes of death worldwide. Apart from genetic factors, the sex hormone estrogen plays a pivotal role in breast cancer development. We are exposed to a plethora of estrogen mimics on a daily basis via various routes. Nevertheless, how xenoestrogens, the exogenous estrogen mimics, modulate cancer-associated signaling pathways and interact with specific genes is still underexplored. Hence, this study aims to explore the direct or indirect binding partners of xenoestrogens and their expression upon exposure to these estrogenic compounds.
METHODS: The collection of genes linked to the xenoestrogens Octylphenol, Nonylphenol, Bisphenol-A, and 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane were gathered from the Comparative Toxicogenomics Database. Venny 2.1 was utilized to pinpoint the genes shared by these xenoestrogens. Subsequently, the shared genes underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery bioinformatics resource. A xenoestrogen-protein interaction network was constructed using Search Tool for Interactions of Chemicals. The expressions of common genes were studied with the microarray dataset GSE5200 from the Gene Expression Omnibus database. Also, the expression of a common gene set within different breast cancer subtypes was identified using the University of California, Santa Cruz Xena.
RESULTS: The genes linked to xenoestrogens were identified, and 13 genes were found to interact with all four xenoestrogens. Through DAVID analysis, the genes chosen are found to be enriched for various functions and pathways, including pathways in cancer, chemical carcinogenesis-receptor activation, and estrogen signaling pathways. The results of the Comparative Toxicogenomics Database and the chemical-protein interaction network derived from STITCH were similar. Microarray data analysis showed significantly high expression of all 13 genes in another study, with Bisphenol-A and Nonylphenol treated MCF-7 cells, most of the genes are expressed in luminal A or basal breast cancer subtype.
CONCLUSIONS: In summary, the genes associated with the four xenoestrogens were mostly linked to pathways related to tumorigenesis, and the expression of these genes was found to be higher in breast cancer.
METHODS: The collection of genes linked to the xenoestrogens Octylphenol, Nonylphenol, Bisphenol-A, and 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane were gathered from the Comparative Toxicogenomics Database. Venny 2.1 was utilized to pinpoint the genes shared by these xenoestrogens. Subsequently, the shared genes underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery bioinformatics resource. A xenoestrogen-protein interaction network was constructed using Search Tool for Interactions of Chemicals. The expressions of common genes were studied with the microarray dataset GSE5200 from the Gene Expression Omnibus database. Also, the expression of a common gene set within different breast cancer subtypes was identified using the University of California, Santa Cruz Xena.
RESULTS: The genes linked to xenoestrogens were identified, and 13 genes were found to interact with all four xenoestrogens. Through DAVID analysis, the genes chosen are found to be enriched for various functions and pathways, including pathways in cancer, chemical carcinogenesis-receptor activation, and estrogen signaling pathways. The results of the Comparative Toxicogenomics Database and the chemical-protein interaction network derived from STITCH were similar. Microarray data analysis showed significantly high expression of all 13 genes in another study, with Bisphenol-A and Nonylphenol treated MCF-7 cells, most of the genes are expressed in luminal A or basal breast cancer subtype.
CONCLUSIONS: In summary, the genes associated with the four xenoestrogens were mostly linked to pathways related to tumorigenesis, and the expression of these genes was found to be higher in breast cancer.
摘要：
背景：乳腺癌是全球死亡的主要原因之一。除了遗传因素,性激素雌激素在乳腺癌的发展中起着举足轻重的作用。我们每天通过各种途径接触大量的雌激素模拟物。然而，如何异种雌激素，外源性雌激素模拟物，调节癌症相关的信号通路和与特定基因的相互作用仍未得到充分研究。因此，本研究旨在探讨异种雌激素的直接或间接结合配偶体及其在暴露于这些雌激素化合物时的表达。
方法：收集与异雌激素辛基酚相关的基因，壬基酚,双酚A,和2,2-双(4-羟基苯基)-1,1,1-三氯乙烷是从比较毒性基因组学数据库收集的。Venny2.1用于查明这些异种雌激素共有的基因。随后，使用注释数据库对共享基因进行了基因本体论和京都基因百科全书以及基因组途径分析，可视化,和集成发现生物信息学资源。使用化学物质相互作用的搜索工具构建了异种雌激素-蛋白质相互作用网络。使用来自基因表达综合数据库的微阵列数据集GSE5200研究常见基因的表达。此外，使用加利福尼亚大学鉴定了不同乳腺癌亚型中常见基因的表达，圣克鲁斯·西娜.
结果：鉴定了与异种雌激素相关的基因，发现13个基因与所有4种异种雌激素相互作用。通过DAVID分析,所选择的基因被发现富含各种功能和途径，包括癌症的途径，化学致癌-受体激活，和雌激素信号通路。比较毒理基因组学数据库和源自STITCH的化学-蛋白质相互作用网络的结果相似。微阵列数据分析显示，在另一项研究中，所有13个基因的显著高表达，用双酚A和壬基酚处理的MCF-7细胞，大多数基因在管腔A或基底乳腺癌亚型中表达。
结论：总之，与四种异种雌激素相关的基因大多与肿瘤发生相关的途径有关，发现这些基因在乳腺癌中的表达更高。
方法：收集与异雌激素辛基酚相关的基因，壬基酚,双酚A,和2,2-双(4-羟基苯基)-1,1,1-三氯乙烷是从比较毒性基因组学数据库收集的。Venny2.1用于查明这些异种雌激素共有的基因。随后，使用注释数据库对共享基因进行了基因本体论和京都基因百科全书以及基因组途径分析，可视化,和集成发现生物信息学资源。使用化学物质相互作用的搜索工具构建了异种雌激素-蛋白质相互作用网络。使用来自基因表达综合数据库的微阵列数据集GSE5200研究常见基因的表达。此外，使用加利福尼亚大学鉴定了不同乳腺癌亚型中常见基因的表达，圣克鲁斯·西娜.
结果：鉴定了与异种雌激素相关的基因，发现13个基因与所有4种异种雌激素相互作用。通过DAVID分析,所选择的基因被发现富含各种功能和途径，包括癌症的途径，化学致癌-受体激活，和雌激素信号通路。比较毒理基因组学数据库和源自STITCH的化学-蛋白质相互作用网络的结果相似。微阵列数据分析显示，在另一项研究中，所有13个基因的显著高表达，用双酚A和壬基酚处理的MCF-7细胞，大多数基因在管腔A或基底乳腺癌亚型中表达。
结论：总之，与四种异种雌激素相关的基因大多与肿瘤发生相关的途径有关，发现这些基因在乳腺癌中的表达更高。
