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This study uses WebGestalt gene ontology functional annotation and enrichment analysis across Reactome and KEGG (2023–2024), evaluates gene interactions via GeneMANIA, and estimates mRNA expression using GEO. Differentially expressed genes are screened with R packages and validated on microarray datasets (GSE37751, GSE42568). Results highlight MMP9, MMP14, and VEGFA upregulation and reveal enriched pathways such as extracellular matrix and AGE-RAGE signaling. Findings support angiogenesis-linked hub genes as potential therapeutic targets or biomarkers.",{"@graph":69,"@context":121},[70,84,104],{"@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/expression-analysis-of-vegf-related-hub-genes-and-pathways-in-breast-cancer-a-comprehensive-bioinformatics-analysis/344843/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/expression-analysis-of-vegf-related-hub-genes-and-pathways-in-breast-cancer-a-comprehensive-bioinformatics-analysis/344843.png","ImageObject",300,407,{"name":92,"@type":93},"Olivia Brown","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-22",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"Which bioinformatics resources were used to identify pathways and gene functions?","Question",{"text":111,"@type":112},"WebGestalt was used for Gene Ontology functional annotation and Reactome/KEGG enrichment. GeneMANIA assessed gene/protein interactions and related network features.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"What were the main differential expression findings among the analyzed genes?",{"text":116,"@type":112},"MMP9 showed the greatest change, while MMP14 and VEGFA had significant increases. Other genes such as APOE, HIF1A, and TNF showed minimal expression changes, and IL1A had a slight increase.",{"name":118,"@type":109,"acceptedAnswer":119},"How were gene expression changes validated?",{"text":120,"@type":112},"Validation used microarray analyses on the GSE37751 and GSE42568 datasets, producing consistent and significant results for multiple studied genes.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},344843,1790075989,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"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},16904993612988,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","IJMS  \nVol 51, No 2, February 2026  \nOriginal Article  \nExpression Analysis of VEGF-Related Hub Genes and Pathways in Breast Cancer: A Comprehensive Bioinformatics Analysis  \nMohadeseh Khoshandam1, PhD; Mohammad Rahmanian2,3 , MD; Mohammad Taghi Hedayati Goudarzi4 , MD; Hossein Soltaninejad5 , PhD; Sadegh Babashah6 , PhD; Mahdiye Khoshandam7, MSc  \n1Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran;  \n2Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran;  \n3Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;  \n4Department of Cardiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran;  \n5 Department of Stem Cells Technology and Tissue Regeneration, Faculty of Interdisciplinary Science and Technologies, Tarbiat Modares University, Tehran, Iran;  \n6 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran; 7Department of Cell Biology and Regenerative Medicine, Academic Center for Education, Culture and Research, Qom Branch, Qom, Iran  \nCorrespondence:  \nHossein Soltaninejad, PhD;  \nDepartment of Stem Cells Technology and Tissue Regeneration, Faculty of Interdisciplinary Science and Technologies, Tarbiat Modares University, Jalal Al Ahmad Hwy. , Nasr Bridge, Postal code: 14155- 6559, Tehran, Iran  \nTel: +98 21 82884041  \nEmail: [hosoltaninejad@gmail.com](hosoltaninejad@gmail.com)  \n[Received: 07 April 2025](Received: 07 April 2025)  \n[Revised: 14 July 2025](Revised: 14 July 2025)  \n[Accepted: 24 August 2025](Accepted: 24 August 2025)  \n\n| \u003Cbr>What’s Known\u003Cbr>• The literature highlights the central role of angiogenesis in tumor progression, metastasis, and therapeutic resistance.\u003Cbr>\u003Cbr>What’s New |\n| --- |\n| • Interaction network analysis identified MMP9, VEGFA, HIF1A, APOE, TNF, IL1A, MMP14 , and TNF as central hub genes with extensive interactions across co-expression, physical interactions, and shared pathways. The results predict that the hub genes correlated with angiogenesis may serve as potential therapeutic targets or could be biomarkers for breast cancer. |\n\nAbstract  \nBackground: Breast cancer is the most common form of cancer among women worldwide, and the rates of both new cases and deaths have increased over the past two decades. The aim of the study was to identify and validate molecular pathways that could potentially be targeted for therapeutic interventions. Methods: The bioinformatics resource WebGestalt was used to determine the functional annotation of the Gene Ontology, as well as enrichment analysis of Reactome and KEGG pathways in 2023-2024. GeneMANIA, a server for assessing proteingene interactions, co-localization, pathways, co-expression, and protein-domain similarity of target genes and their interacting genes, was evaluated via this web tool. GEO was also used to determine mRNA expression levels in BRCA individuals. R packages were used to screen for differentially expressed genes for both datasets. On the other hand, the open cancer resources GENT2 TNMPlot, UCSCXena, ENCORI platform, BioXpress, OncoDB, OncoMX, and GEPIA2 were used to measure the differential expression of mRNAs in BRCA patients.  \nResults: Among the genes analyzed, matrix metalloproteinase-9 (MMP9) showed the greatest change. Similarly, matrix metallopeptidase 14 (MMP14) and Endogenous Vascular Endothelial Growth Factor-A (VEGFA) showed significant increases. Other up-regulated genes, including Apolipoprotein E (APOE), Hypoxia-Inducible Factor-1 Alpha (HIF1A), and Tumor Necrosis Factor (TNF) showed minimal expression changes with minor fluctuations. Finally, Interleukin-1 alpha precursor (IL1A) exhibited a slight increase in expression. Validation of gene expression changes through microarray studies on the GSE37751 and GS","cbCaiceCGcalZLNO","https://ap.wps.com/l/cbCaiceCGcalZLNO","pdf",1955214,11,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Keywords\n# Introduction","[{\"question\":\"Which bioinformatics resources were used to identify pathways and gene functions?\",\"answer\":\"WebGestalt was used for Gene Ontology functional annotation and Reactome/KEGG enrichment. GeneMANIA assessed gene/protein interactions and related network features.\"},{\"question\":\"What were the main differential expression findings among the analyzed genes?\",\"answer\":\"MMP9 showed the greatest change, while MMP14 and VEGFA had significant increases. Other genes such as APOE, HIF1A, and TNF showed minimal expression changes, and IL1A had a slight increase.\"},{\"question\":\"How were gene expression changes validated?\",\"answer\":\"Validation used microarray analyses on the GSE37751 and GSE42568 datasets, producing consistent and significant results for multiple studied genes.\"}]","Expression Analysis of VEGF-Related Hub Genes and Pathways in Breast Cancer: A Comprehensive Bioinformatics Analysis | PDF",1790055446,28]