Identification of mitophagy-related key genes and their correlation with immune cell infiltration in acute myocardial infarction via bioinformatics analysis

被引:0
作者
Sheng, Zulong [1 ]
Zhang, Rui [1 ]
Ji, Zhenjun [1 ]
Liu, Zhuyuan [1 ]
Zhou, Yaqing [1 ]
机构
[1] Southeast Univ, Zhongda Hosp, Med Sch, Dept Cardiol, Nanjing, Peoples R China
关键词
mitophagy; acute myocardial infarction; bioinformatics analysis; biomarkers; diagnostic risk model; SEMANTIC SIMILARITY; R PACKAGE; INJURY; GEO;
D O I
10.3389/fcvm.2024.1501608
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Acute myocardial infarction (AMI), a subset of acute coronary syndrome, remains the major cause of mortality worldwide. Mitochondrial dysfunction is critically involved in AMI progression, and mitophagy plays a vital role in eliminating damaged mitochondria. This study aimed to explore mitophagy-related biomarkers and their potential molecular basis in AMI.Methods AMI datasets (GSE24519 and GSE34198) from the Gene Expression Omnibus database were combined and the batch effects were removed. Differentially expressed genes (DEGs) in AMI were selected, intersected with mitophagy-related genes for mitophagy-related DEGs (MRDEGs), and then subjected to enrichment analyses. Next, the MRDEGs were screened using machine learning methods (logistic regression analysis, RandomForest, least absolute shrinkage and selection operator) to construct a diagnostic risk model and select the key genes in AMI. The diagnostic efficacy of the model was evaluated using a nomogram. Moreover, the infiltration patterns of different immune cells in two risk groups were compared. We also explored the interactions between the key genes themselves or with miRNAs/transcription factors (TFs) and drug compounds and visualized the protein structure of the key genes. Finally, we explored and validated the expression of key genes in plasma samples of patients with an AMI and healthy individuals.Results We screened 28 MRDEGs in AMI. Based on machine learning methods, 12 key genes were screened for the diagnostic risk model, including AGPS, CA2, CAT, LTA4H, MYO9B, PRDX6, PYGB, SIRT3, TFEB, TOM1, UBA52, and UBB. The nomogram further revealed the accuracy of the model for AMI diagnosis. Moreover, we found a lower abundance of immune cells such as gamma delta T and natural killer cells in the high-risk group, and the expression of key genes showed a significant correlation with immune infiltration levels in both groups. Finally, 64 miRNA-mRNA pairs, 75 TF-mRNA pairs, 119 RNA-binding protein-mRNA pairs, and 32 drug-mRNA pairs were obtained in the interaction networks.Conclusions In total, 12 key MRDEGs were identified and a risk model was constructed for AMI diagnosis. The findings of this study might provide novel biomarkers for improving the detection of AMI.
引用
收藏
页数:20
相关论文
共 66 条
[1]   Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure [J].
Abudureyimu, Miyesaier ;
Yu, Wenjun ;
Cao, Richard Yang ;
Zhang, Yingmei ;
Liu, Haibo ;
Zheng, Hongchao .
FRONTIERS IN PHYSIOLOGY, 2020, 11
[2]   Mitophagy in cardiovascular diseases: molecular mechanisms, pathogenesis, and treatment [J].
Ajoolabady, Amir ;
Chiong, Mario ;
Lavandero, Sergio ;
Klionsky, Daniel J. ;
Ren, Jun .
TRENDS IN MOLECULAR MEDICINE, 2022, 28 (10) :836-849
[3]   Cardiomyocyte-Specific JunD Overexpression Increases Infarct Size following Ischemia/Reperfusion Cardiac Injury by Downregulating Sirt3 [J].
Akhmedov, Alexander ;
Montecucco, Fabrizio ;
Costantino, Sarah ;
Vdovenko, Daria ;
Clerigue, Ariane Schaub ;
Gaul, Daniel S. ;
Burger, Fabienne ;
Roth, Aline ;
Carbone, Federico ;
Liberale, Luca ;
Amrollahi-Sharifabadi, Mohammad ;
Vellone, Valerio Gaetano ;
Eriksson, Urs ;
Matter, Christian M. ;
Crowe, Lindsey A. ;
Vallee, Jean-Paul ;
Paneni, Francesco ;
Vanhoutte, Paul M. ;
Camici, Giovanni G. ;
Mach, Francois ;
Luscher, Thomas F. .
THROMBOSIS AND HAEMOSTASIS, 2020, 120 (01) :168-180
[4]   Acute Myocardial Infarction [J].
Anderson, Jeffrey L. ;
Morrow, David A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (21) :2053-2064
[5]   NCBI GEO: archive for functional genomics data sets-update [J].
Barrett, Tanya ;
Wilhite, Stephen E. ;
Ledoux, Pierre ;
Evangelista, Carlos ;
Kim, Irene F. ;
Tomashevsky, Maxim ;
Marshall, Kimberly A. ;
Phillippy, Katherine H. ;
Sherman, Patti M. ;
Holko, Michelle ;
Yefanov, Andrey ;
Lee, Hyeseung ;
Zhang, Naigong ;
Robertson, Cynthia L. ;
Serova, Nadezhda ;
Davis, Sean ;
Soboleva, Alexandra .
NUCLEIC ACIDS RESEARCH, 2013, 41 (D1) :D991-D995
[6]   Diagnosis and Treatment of Acute Coronary Syndromes A Review [J].
Bhatt, Deepak L. ;
Lopes, Renato D. ;
Harrington, Robert A. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2022, 327 (07) :662-675
[7]   Random forests [J].
Breiman, L .
MACHINE LEARNING, 2001, 45 (01) :5-32
[8]   Mitochondrial dysfunction in macrophages promotes inflammation and suppresses repair after myocardial infarction [J].
Cai, Shanshan ;
Zhao, Mingyue ;
Zhou, Bo ;
Yoshii, Akira ;
Bugg, Darrian ;
Villet, Outi ;
Sahu, Anita ;
Olson, Gregory S. ;
Davis, Jennifer ;
Tian, Rong .
JOURNAL OF CLINICAL INVESTIGATION, 2023, 133 (04)
[9]   Mitochondrial Dynamics and Its Involvement in Disease [J].
Chan, David C. .
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 15, 2020, 2020, 15 :235-259
[10]  
Chen BB, 2018, METHODS MOL BIOL, V1711, P243, DOI 10.1007/978-1-4939-7493-1_12