Roles of Immune and Oxidative Stress-Related Factors in the Diagnosis of Coronary Artery Disease: A Retrospective Study
DOI:
https://doi.org/10.59958/hsf.5799Keywords:
coronary artery disease, immune, oxidative stress, biomarkers, coronary artery disease diagnosis, bioinformatics analysis technologyAbstract
Background: Coronary artery disease (CAD) is one of the main causes of sudden death, but its exact pathogenesis requires further study. Thus, this study aimed to explore the immune and oxidative stress-related factors in CAD progression and their roles in CAD diagnosis. Methods: Bioinformatics analysis was used in this study, and the GSE23561 dataset (training set) we used contained the transcriptome sequencing results of six CAD peripheral blood samples and nine control samples. The data were obtained and analysed by querying the Gene Expression Omnibus database. First, the differentially expressed immune and oxidative stress-related genes (DEIOGs) between the groups were identified. DEIOGs were then analysed based on Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A protein—protein interaction (PPI) network for DEIOGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and hub genes were identified through the PPI network. Moreover, transcription factors and microRNAs (miRNAs) targeting hub genes were identified to explore the potential regulatory mechanisms of hub genes. The receiver operating characteristic (ROC) curve analysis was constructed to examine the role of hub genes in CAD diagnosis. Finally, the data of GSE23561 (validated set) were used to validate the diagnostic potential of these hub genes. Results: Primarily, 66 DEIOGs were identified, which are involved in many important pathways related to CAD, such as the “mitogen-activated protein kinase (MAPK) signalling pathway” and “lipid and atherosclerosis”. A PPI network of DEIOGs was then constructed, and 10 hub genes were identified sequentially. A total of 37 transcription factors and 481 miRNAs that played important roles in hub genes regulation were identified. The ROC curves indicated that five special hub genes (Fos, Il6, Jun, Mapk3, and Mmp9) could serve as potential diagnostic biomarkers for CAD. Conclusions: Bioinformatics analysis technology was used to identify 10 hub DEIOGs that might play a crucial role in CAD progression, and five special hub genes (Fos, Il6, Jun, Mapk3, and Mmp9) could be regarded as potential biomarkers for CAD diagnosis. However, further studies are required to verify the functions of these hub genes.
References
Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S. A review on coronary artery disease, its risk factors, and therapeutics. Journal of Cellular Physiology. 2019; 234: 16812–16823.
Kantaria M, Buleishvili M, Kipiani NV, Ormotsadze G, Sanikidze T. RISK-FACTORS OF CORONARY ARTERY DISEASE (REVIEW). Georgian Medical News. 2020; 78–82.
Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation. 2005; 111: 3481–3488.
Inoue N. Vascular C-reactive protein in the pathogenesis of coronary artery disease: role of vascular inflammation and oxidative stress. Cardiovascular & Hematological Disorders Drug Targets. 2006; 6: 227–231.
Chaikijurajai T, Tang WHW. Myeloperoxidase: a potential therapeutic target for coronary artery disease. Expert Opinion on Therapeutic Targets. 2020; 24: 695–705.
Chen H, Luo J, Guo J. Development and validation of a five-immune gene prognostic risk model in colon cancer. BMC Cancer. 2020; 20: 395.
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research. 2015; 43: e47.
Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics: a Journal of Integrative Biology. 2012; 16: 284–287.
von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B. STRING: a database of predicted functional associations between proteins. Nucleic Acids Research. 2003; 31: 258–261.
Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Systems Biology. 2014; 8: S11.
Fornes O, Castro-Mondragon JA, Khan A, van der Lee R, Zhang X, Richmond PA, et al. JASPAR 2020: update of the open-access database of transcription factor binding profiles. Nucleic Acids Research. 2020; 48: D87–D92.
Chang L, Zhou G, Soufan O, Xia J. miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology. Nucleic Acids Research. 2020; 48: W244–W251.
Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011; 12: 77.
Obuchowski NA, Bullen JA. Receiver operating characteristic (ROC) curves: review of methods with applications in diagnostic medicine. Physics in Medicine and Biology. 2018; 63: 07TR01.
Hueso M, Mallén A, Casas Á, Guiteras J, Sbraga F, Blasco-Lucas A, et al. Integrated miRNA/mRNA Counter-Expression Analysis Highlights Oxidative Stress-Related Genes CCR7 and FOXO1 as Blood Markers of Coronary Arterial Disease. International Journal of Molecular Sciences. 2020; 21: 1943.
Ji N, Qi Z, Wang Y, Yang X, Yan Z, Li M, et al. Pyroptosis: A New Regulating Mechanism in Cardiovascular Disease. Journal of Inflammation Research. 2021; 14: 2647–2666.
Ohmori T, Yamaoka T, Ando K, Kusumoto S, Kishino Y, Manabe R, et al. Molecular and Clinical Features of EGFR-TKI-Associated Lung Injury. International Journal of Molecular Sciences. 2021; 22: 792.
Medda N, De SK, Maiti S. Different mechanisms of arsenic related signaling in cellular proliferation, apoptosis and neo-plastic transformation. Ecotoxicology and Environmental Safety. 2021; 208: 111752.
Saraiva M, Vieira P, O'Garra A. Biology and therapeutic potential of interleukin-10. The Journal of Experimental Medicine. 2020; 217: e20190418.
Hirano T. IL-6 in inflammation, autoimmunity and cancer. International Immunology. 2021; 33: 127–148.
Papavassiliou AG, Musti AM. The Multifaceted Output of c-Jun Biological Activity: Focus at the Junction of CD8 T Cell Activation and Exhaustion. Cells. 2020; 9: 2470.
Alvarez-Bolado G. Development of neuroendocrine neurons in the mammalian hypothalamus. Cell and Tissue Research. 2019; 375: 23–39.
Wang H, Pang W, Xu X, You B, Zhang C, Li D. Cryptotanshinone Attenuates Ischemia/Reperfusion-induced Apoptosis in Myocardium by Upregulating MAPK3. Journal of Cardiovascular Pharmacology. 2021; 77: 370–377.
Zhang H, Liu L, Jiang C, Pan K, Deng J, Wan C. MMP9 protects against LPS-induced inflammation in osteoblasts. Innate Immunity. 2020; 26: 259–269.
Brian BF 4th, Freedman TS. The Src-family Kinase Lyn in Immunoreceptor Signaling. Endocrinology. 2021; 162: bqab152.
Pan CS, Yan L, Lin SQ, He K, Cui YC, Liu YY, et al. QiShenYiQi Pills Attenuates Ischemia/Reperfusion-Induced Cardiac Microvascular Hyperpermeability Implicating Src/Caveolin-1 and RhoA/ROCK/MLC Signaling. Frontiers in Physiology. 2021; 12: 753761.
Si R, Zhang Q, Tsuji-Hosokawa A, Watanabe M, Willson C, Lai N, et al. Overexpression of p53 due to excess protein O-GlcNAcylation is associated with coronary microvascular disease in type 2 diabetes. Cardiovascular Research. 2020; 116: 1186–1198.
Bernard E, Nannya Y, Hasserjian RP, Devlin SM, Tuechler H, Medina-Martinez JS, et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nature Medicine. 2020; 26: 1549–1556.
Jia S, Liu Y, Yuan J. Evidence in Guidelines for Treatment of Coronary Artery Disease. Advances in Experimental Medicine and Biology. 2020; 1177: 37–73.
Doenst T, Haverich A, Serruys P, Bonow RO, Kappetein P, Falk V, et al. PCI and CABG for Treating Stable Coronary Artery Disease: JACC Review Topic of the Week. Journal of the American College of Cardiology. 2019; 73: 964–976
Pyxaras SA, Wijns W, Reiber JHC, Bax JJ. Invasive assessment of coronary artery disease. Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology. 2018; 25: 860–871.
Barone-Rochette G, Bruère D, Mansencal N. How to explore coronary artery disease? Archives of Cardiovascular Diseases. 2019; 112: 546–549.
Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, et al. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019; 139: e891–e908.