Si Yan, Zhichao Fang, Xin Xue, Can Hou, Xiaoyu Yang
{"title":"Identification of Hypoxia-Related Genes in Human Myocardial Infarction and Cancers.","authors":"Si Yan, Zhichao Fang, Xin Xue, Can Hou, Xiaoyu Yang","doi":"10.1159/000547896","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Myocardial infarction (MI) and cancer collectively account for over 50% of global mortality. Recent studies have revealed multiple associations between these two diseases, including chronic inflammation and oxidative stress, with particular focus on hypoxia-mediated signaling pathways. In ischemic myocardium, oxygen deprivation triggers apoptosis, fibrosis, and pathological tissue reorganization; in the tumor microenvironment (TME), hypoxia drives angiogenesis, metabolic reprogramming, and immune evasion. Thus, identifying differentially expressed genes related to hypoxia in MI may provide new targets for the treatment of MI and cancer.</p><p><strong>Methods: </strong>The specimens from MI patients in this study were retrieved from the Gene Expression Omnibus (GEO) database. Using the \"limma\" package in R and weighted gene co-expression network analysis (WGCNA), a set of hypoxia-related differentially expressed genes was screened out. Subsequently, these hub genes were subjected to functional enrichment analysis, and their expression levels were verified in an independent dataset. Finally, transcriptional regulatory analysis and immune infiltration analysis were conducted for the hub genes, and their expression levels and prognostic values in various cancers were evaluated.</p><p><strong>Results: </strong>In MI samples, nine genes, namely Immediate Early Response 3 (IER3), Heme Oxygenase 1 (HMOX1), Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A), Plasminogen Activator Urokinase Receptor (PLAUR), MAF BZIP Transcription Factor F (MAFF), Solute Carrier Family 2 Member 3 (SLC2A3), Jun Proto-Oncogene (JUN), Transforming Growth Factor Beta Induced (TGFBI), and 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), were found to demonstrate significant dysregulation and to be closely associated with the occurrence of various cancers. Pan-cancer analysis further revealed the association of hub genes with cancer prognosis. Immune analysis also revealed their associations with resting CD4+ memory T cells and gamma delta T cells in TME.</p><p><strong>Conclusion: </strong>IER3, HMOX1, CDKN1A, PLAUR, MAFF, SLC2A3, JUN, TGFBI, and PFKFB3 are potential biomarkers for MI and cancer. Research on hypoxia-related genes may provide new therapeutic targets for these two diseases.</p>","PeriodicalId":9391,"journal":{"name":"Cardiology","volume":" ","pages":"1-23"},"PeriodicalIF":1.7000,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503813/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000547896","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Myocardial infarction (MI) and cancer collectively account for over 50% of global mortality. Recent studies have revealed multiple associations between these two diseases, including chronic inflammation and oxidative stress, with particular focus on hypoxia-mediated signaling pathways. In ischemic myocardium, oxygen deprivation triggers apoptosis, fibrosis, and pathological tissue reorganization; in the tumor microenvironment (TME), hypoxia drives angiogenesis, metabolic reprogramming, and immune evasion. Thus, identifying differentially expressed genes related to hypoxia in MI may provide new targets for the treatment of MI and cancer.
Methods: The specimens from MI patients in this study were retrieved from the Gene Expression Omnibus (GEO) database. Using the "limma" package in R and weighted gene co-expression network analysis (WGCNA), a set of hypoxia-related differentially expressed genes was screened out. Subsequently, these hub genes were subjected to functional enrichment analysis, and their expression levels were verified in an independent dataset. Finally, transcriptional regulatory analysis and immune infiltration analysis were conducted for the hub genes, and their expression levels and prognostic values in various cancers were evaluated.
Results: In MI samples, nine genes, namely Immediate Early Response 3 (IER3), Heme Oxygenase 1 (HMOX1), Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A), Plasminogen Activator Urokinase Receptor (PLAUR), MAF BZIP Transcription Factor F (MAFF), Solute Carrier Family 2 Member 3 (SLC2A3), Jun Proto-Oncogene (JUN), Transforming Growth Factor Beta Induced (TGFBI), and 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), were found to demonstrate significant dysregulation and to be closely associated with the occurrence of various cancers. Pan-cancer analysis further revealed the association of hub genes with cancer prognosis. Immune analysis also revealed their associations with resting CD4+ memory T cells and gamma delta T cells in TME.
Conclusion: IER3, HMOX1, CDKN1A, PLAUR, MAFF, SLC2A3, JUN, TGFBI, and PFKFB3 are potential biomarkers for MI and cancer. Research on hypoxia-related genes may provide new therapeutic targets for these two diseases.
期刊介绍：
''Cardiology'' features first reports on original clinical, preclinical and fundamental research as well as ''Novel Insights from Clinical Experience'' and topical comprehensive reviews in selected areas of cardiovascular disease. ''Editorial Comments'' provide a critical but positive evaluation of a recent article. Papers not only describe but offer critical appraisals of new developments in non-invasive and invasive diagnostic methods and in pharmacologic, nutritional and mechanical/surgical therapies. Readers are thus kept informed of current strategies in the prevention, recognition and treatment of heart disease. Special sections in a variety of subspecialty areas reinforce the journal''s value as a complete record of recent progress for all cardiologists, internists, cardiac surgeons, clinical physiologists, pharmacologists and professionals in other areas of medicine interested in current activity in cardiovascular diseases.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
