[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-380905-105":59,"doc-detail-380905-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","endocrine-disrupting-chemicals-influence-hub-genes-associated-with-aggressive-prostate-cancer","Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer","","Prostate cancer (PCa) remains difficult to prevent due to an incomplete mechanistic understanding of how environmental chemical exposures drive aggressive disease. This study identifies endocrine-disrupting chemicals (EDCs) linked to PCa hub genes and their transcription factors, integrating protein–protein interaction network analysis. Six PCa microarray datasets (GSE46602, GSE38241, GSE69223, GSE32571, GSE55945, GSE26126) were analyzed to select differentially expressed genes with |log2FC| ≥ 1 and adjusted p \u003C 0.05, followed by functional enrichment and RNA-seq validation using TCGA.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/endocrine-disrupting-chemicals-influence-hub-genes-associated-with-aggressive-prostate-cancer/380905/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/endocrine-disrupting-chemicals-influence-hub-genes-associated-with-aggressive-prostate-cancer/380905.png","ImageObject",300,407,{"name":92,"@type":93},"pixelkiddo","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the goal of this research on endocrine-disrupting chemicals and prostate cancer?","Question",{"text":112,"@type":113},"To identify endocrine-disrupting chemicals associated with prostate cancer hub genes and/or transcription factors, and to relate them to hub-gene protein–protein interaction networks.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were differentially expressed genes selected in the study?",{"text":117,"@type":113},"From six PCa microarray datasets, genes were chosen using |log2FC| ≥ 1 and an adjusted p-value \u003C 0.05.",{"name":119,"@type":110,"acceptedAnswer":120},"What role did TCGA and the chemical toxicogenomic database (CTD) play?",{"text":121,"@type":113},"TCGA RNA-seq data (cases and controls) validated the association of identified hub genes, while CTD was used to extrapolate environmental chemical exposure influences and map recognized EDCs to transcription factors binding the hub genes.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},380905,1790367213,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":41,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},962090883892,"https://ap-avatar.wpscdn.com/avatar/e00115db34f3e0f11b?x-image-process=image/resize,m_fixed,w_180,h_180&k=1790152879550218658","Article  \nEndocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer  \nDiaaidden Alwadi 1, Quentin Felty 1, Changwon Yoo 2, Deodutta Roy 1 and Alok Deoraj 1, *  \nCitation: Alwadi, D.; Felty, Q.; Yoo, C.; Roy, D.; Deoraj, A. Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer. Int. J. Mol. Sci. 2023, 24, 3191. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24043191  \nAcademic Editor: Dariusz Szukiewicz  \nReceived: 20 December 2022  \nRevised: 25 January 2023  \nAccepted: 30 January 2023  \nPublished: 6 February 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA  \n2 Department of Biostatistics, Florida International University, Miami, FL 33199, USA  \n* Correspondence: adeoraj@fi[u.edu](u.edu)  \nAbstract: Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men in the world. Its prevention has been limited because of an incomplete understanding of how environmental exposures to chemicals contribute to the molecular pathogenesis of aggressive PCa. Environmental exposures to endocrine-disrupting chemicals (EDCs) may mimic hormones involved in PCa development. This research aims to identify EDCs associated with PCa hub genes and/or transcription factors (TF) of these hub genes in addition to their protein–protein interaction (PPI) network. We are expanding upon the scope of our previous work, using six PCa microarray datasets, namely, GSE46602, GSE38241, GSE69223, GSE32571, GSE55945, and GSE26126, from the NCBI/GEO, to select differentially expressed genes based on | log2FC | (fold change) 􀀕 1 and an adjusted p-value \u003C 0.05 . An integrated bioinformatics analysis was used for enrichment analysis (using DAVID.6.8, GO, KEGG, STRING, MCODE, CytoHubba, and GeneMANIA) . Next, we validated the association of these PCa hub genes in RNA-seq PCa cases and controls from TCGA. The influence of environmental chemical exposures, including EDCs, was extrapolated using the chemical toxicogenomic database (CTD) . A total of 369 overlapping DEGs were identified associated with biological processes, such as cancer pathways, cell division, response to estradiol, peptide hormone processing, and the p53 signaling pathway. Enrichment analysis revealed five up-regulated (NCAPG, MKI67, TPX2, CCNA2, CCNB1) and seven down-regulated (CDK1, CCNB2, AURKA, UBE2C, BUB1B, CENPF, RRM2) hub gene expressions. Expression levels of these hub genes were significant in PCa tissues with high Gleason scores 􀀕 7. These identified hub genes influenced disease-free survival and overall survival of patients 60–80 years of age. The CTD studies showed 17 recognized EDCs that affect TFs (NFY, CETS1P54, OLF1, SRF, COMP1) that are known to bind to our PCa hub genes, namely, NCAPG, MKI67, CCNA2, CDK1, UBE2C, and CENPF. These validated differentially expressed hub genes can be potentially developed as molecular biomarkers with a systems perspective for risk assessment of a wide-ranging list of EDCs that may play overlapping and important role(s) in the prognosis of aggressive PCa.  \nKeywords: endocrine disruptive chemicals; prostate cancer; gene ontology; protein–protein interaction; molecular biomarkers; environmental health risk assessment  \n1. Introduction  \nProstate cancer (PCa) is the second leading cause of cancer death among men in the U.S. [1] and the world [2] . In the U.S., PCa is the most frequently diagnosed cancer (26% of all sites of cancer) and the second leading cause of death in men (11%) after lung cancer (22%) [3,4] . The standard ","cbCaiuT33ak0bOR5","https://ap.wps.com/l/cbCaiuT33ak0bOR5","pdf",10415979,"English","# Abstract\n# Introduction","[{\"question\":\"What is the goal of this research on endocrine-disrupting chemicals and prostate cancer?\",\"answer\":\"To identify endocrine-disrupting chemicals associated with prostate cancer hub genes and/or transcription factors, and to relate them to hub-gene protein–protein interaction networks.\"},{\"question\":\"How were differentially expressed genes selected in the study?\",\"answer\":\"From six PCa microarray datasets, genes were chosen using |log2FC| ≥ 1 and an adjusted p-value \\u003c 0.05.\"},{\"question\":\"What role did TCGA and the chemical toxicogenomic database (CTD) play?\",\"answer\":\"TCGA RNA-seq data (cases and controls) validated the association of identified hub genes, while CTD was used to extrapolate environmental chemical exposure influences and map recognized EDCs to transcription factors binding the hub genes.\"}]","Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer | PDF",1790242698,76]