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Survival analyses across TCGA, GSE4830, and GSE25055 evaluate prognostic value, while clusterProfiler supports enrichment, and functional assays assess ATF4 effects on proliferation and migration. Results indicate reduced ATF4 expression yet significant associations with disease-specific and overall survival, links to immune infiltration and immune-related genomic signatures, and enhanced Treg differentiation in ATF4-high tissues. ATF4 modulates breast cancer cell behavior, suggesting biomarker and therapeutic relevance.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/a-bioinformatic-analysis-found-low-expression-and-clinical-significance-of-atf4-in-breast-cancer/333103/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/a-bioinformatic-analysis-found-low-expression-and-clinical-significance-of-atf4-in-breast-cancer/333103.png","ImageObject",300,407,{"name":42,"@type":43},"Logic","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main goal regarding ATF4 in breast cancer?","Question",{"text":63,"@type":64},"To clarify whether ATF4 expression relates to breast cancer progression, immune microenvironment features, and patient prognosis, and whether ATF4 could serve as a clinically useful biomarker.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was ATF4 expression analyzed in this study?",{"text":68,"@type":64},"The study used TCGA pan-cancer data and breast cancer expression profiles from Gene Expression Omnibus, performed single-cell analysis on ATF4 using two datasets, and used Human Protein Atlas and SpatialDB to demonstrate tissue-level spatial distribution.",{"name":70,"@type":61,"acceptedAnswer":71},"What immune-related findings connect ATF4 to breast cancer outcomes?",{"text":72,"@type":64},"Higher ATF4 expression correlates positively with immune infiltration levels and immune-related genomic signatures. Elevated ATF4 is linked to increased differentiation of T cells into regulatory T (Treg) cells within ATF4-high tissues.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},333103,1790962530,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":112,"preview_page_count":4},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","Heliyon 10 (2024) e24669  \nContents lists available at ScienceDirect  \nHeliyon  \njournal [homepage:](homepage: www.cell.com/heliyon)[ www.cell.com/heliyon](homepage: www.cell.com/heliyon)  \nResearch article  \nA bioinformatic analysis found low expression and clinical significance of ATF4 in breast cancer  \nLujing Shao a, 1, Zhounan Zhu a, 1, Xinyan Jiab, 1, Yabin Mac, **, Chunyan Donga, * a Department of Oncology, East Hospital Affiliated to Tongji University, Tongji University School of Medicine, Tongji University, Shanghai, 200092, PR China  \nb Jinzhou Medical University, Jinzhou, Liaoning, 121000, PR China  \nc Department of Pharmacy, East Hospital Affiliated to Tongji University, Tongji University School of Medicine, Tongji University, Shanghai, 200092, PR China  \nA R T I C L E I N F O  \nKeywords: ATF4  \nBreast cancer MDA-MB-231 Treg Biomarker  \nA B S T R A C T  \nBackground: Activating Transcription Factor 4 (ATF4) expression exhibits differential patterns across different types of tumors. Besides, the pathogenesis of breast cancer is complex, and the exact relationship between ATF4 and ATF4 remains uncertain.  \nMethods: The analysis of ATF4 expression was conducted by utilizing The Cancer Genome Atlas (TCGA) pan-cancer data, while the gene expression profile of breast cancer was checked by the comprehensive database-Gene Expression Omnibus database. In order to gain a more comprehensive understanding of the specific cell types that exhibit ATF4 expression within the microenvironment of breast cancer, we conducted a single-cell analysis of ATF4 using two distinct datasets of human breast cancer (GSE114717 and GSE11088, respectively). The spatial distribution of ATF4 within a tissue was demonstrated based on datasets obtained from the Human Protein Atlas (HPA) and SpatialDB. The clinical prognostic significance of ATF4 was assessed by analyzing clinical survival data obtained from TCGA, GSE4830, and GSE25055 datasets. We used the R package clusterProfiler to carry out an enrichment analysis of ATF4. We assessed how ATF4 impacts the growth and movement of breast cancer cell lines. We manipulated ATF4 levels using plasmid transfection techniques.  \nResults: The expression of ATF4 was found to be suboptimal and demonstrated a significant correlation with enhanced disease-specific survival (p = 0.012) and overall survival (p = 0.032) in breast cancer as well as other malignancies. We conducted an analysis to investigate the interaction between the infiltration level of immune cells and the expression of ATF4, using samples obtained from TCGA with known immune cell infiltration scores. Furthermore, a notable positive correlation exists between the elevated expression of ATF4 and immune-related genomes, specifically those associated with chemokine as well as immunity. Subsequent examination revealed a notable augmentation in the cytodifferentiation of T cells into regulatory T (Treg) cells within tissues exhibiting elevated levels of ATF4 expression. ATF4 exhibits notable upregulation in the MDA-MB-231 cell, thereby exerting a substantial impact on cell proliferation and migration  \n* Corresponding author. Department of Oncology, East Hospital Affiliated to Tongji University, Tongji University School of Medicine, Tongji University, Shanghai, 200092, PR China.  \n** Corresponding author.  \nE-mail addresses: [slujing94@126.com](slujing94@126.com) (L. Shao), [zhuzhounan@tongji.edu.cn](zhuzhounan@tongji.edu.cn) (Z. Zhu), [J17861170060@163.com](J17861170060@163.com) (X. Jia), [YabinMa23@126.com](YabinMa23@126.com)  \n(Y. Ma), [cy_dong@tongji.edu.cn](cy_dong@tongji.edu.cn) (C. Dong).  \n1 Lujing Shao, Zhounan Zhu and Xinyan Jia contributed equally to this article.  \n[https://doi.org/10.1016/j.heliyon.2024.e24669](https://doi.org/10.1016/j.heliyon.2024.e24669)  \nReceived 8 November 2023; Received in revised form 3 January 2024; Accepted 11 January 2024 Available online 12 January 2024  \n2405-8440/© 2024 The Authors. Published by Elsevier Lt","cbCaikjw8DCtWgRs","https://ap.wps.com/l/cbCaikjw8DCtWgRs","pdf",9742643,12,"English","# Background\n# Methods\n## Data sources and analysis\n## Single-cell, spatial, and survival analyses\n## Enrichment and functional validation\n# Results\n## Prognostic and pan-cancer associations\n## Immune infiltration and immune-related gene links\n## Treg differentiation and cellular effects\n# Conclusions","[{\"question\":\"What is the main goal regarding ATF4 in breast cancer?\",\"answer\":\"To clarify whether ATF4 expression relates to breast cancer progression, immune microenvironment features, and patient prognosis, and whether ATF4 could serve as a clinically useful biomarker.\"},{\"question\":\"How was ATF4 expression analyzed in this study?\",\"answer\":\"The study used TCGA pan-cancer data and breast cancer expression profiles from Gene Expression Omnibus, performed single-cell analysis on ATF4 using two datasets, and used Human Protein Atlas and SpatialDB to demonstrate tissue-level spatial distribution.\"},{\"question\":\"What immune-related findings connect ATF4 to breast cancer outcomes?\",\"answer\":\"Higher ATF4 expression correlates positively with immune infiltration levels and immune-related genomic signatures. Elevated ATF4 is linked to increased differentiation of T cells into regulatory T (Treg) cells within ATF4-high tissues.\"}]","A bioinformatic analysis found low expression and clinical significance of ATF4 in breast cancer | PDF",1790000862]