Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cardiovascular Disorders
Published in: BMC Cardiovascular Disorders 1/2024

Open Access 01-12-2024 | Myocardial Infarction | Research

Integrated analysis and validation of ferroptosis-related genes and immune infiltration in acute myocardial infarction

Authors: Xinyu Wu, Jingru Li, Shengjie Chai, Chaguo Li, Si Lu, Suli Bao, Shuai Yu, Hao Guo, Jie He, Yunzhu Peng, Huang Sun, Luqiao Wang

Published in: BMC Cardiovascular Disorders | Issue 1/2024

Login to get access

Abstract

Background

Acute myocardial infarction (AMI) is indeed a significant cause of mortality and morbidity in individuals with coronary heart disease. Ferroptosis, an iron-dependent cell death, is characterized by the accumulation of intracellular lipid peroxides, which is implicated in cardiomyocyte injury. This study aims to identify biomarkers that are indicative of ferroptosis in the context of AMI, and to examine their potential roles in immune infiltration.

Methods

Firstly, the GSE59867 dataset was used to identify differentially expressed ferroptosis-related genes (DE-FRGs) in AMI. We then performed gene ontology (GO) and functional enrichment analysis on these DE-FRGs. Secondly, we analyzed the GSE76591 dataset and used bioinformatic methods to build ceRNA networks. Thirdly, we identified hub genes in protein–protein interaction (PPI) network. After obtaining the key DE-FRGs through the junction of hub genes with ceRNA and least absolute shrinkage and selection operator (LASSO). ImmucellAI was applied to estimate the immune cell infiltration in each sample and examine the relationship between key DE-FRGs and 24 immunocyte subsets. The diagnostic performance of these genes was further evaluated using the receiver operating characteristic (ROC) curve analysis. Ultimately, we identified an immune-related ceRNA regulatory axis linked to ferroptosis in AMI.

Results

Among 56 DE-FRGs identified in AMI, 41 of them were integrated into the construction of competitive endogenous RNA (ceRNA) networks. TLR4 and PIK3CA were identified as key DE-FRGs and PIK3CA was confirmed as a diagnostic biomarker for AMI. Moreover, CD4_native cells, nTreg cells, Th2 cells, Th17 cells, central-memory cells, effector-memory cells, and CD8_T cells had higher infiltrates in AMI samples compared to control samples. In contrast, exhausted cells, iTreg cells, and Tfh cells had lower infiltrates in AMI samples. Spearman analysis confirmed the correlation between 24 immune cells and PIK3CA/TLR4. Ultimately, we constructed an immune-related regulatory axis involving XIST and OIP5-AS1/miR-216a/PIK3CA.

Conclusion

Our comprehensive analysis has identified PIK3CA as a robust and promising biomarker for this condition. Moreover, we have also identified an immune-related regulatory axis involving XIST and OIP5-AS1/miR-216a/PIK3CA, which may play a key role in regulating ferroptosis during AMI progression.
Appendix
Available only for authorised users
Literature
1.
Wang L, Zhang Y, Yu M, Yuan W. Identification of Hub Genes in the Remodeling of Non-Infarcted Myocardium Following Acute Myocardial Infarction. J Cardiovasc Dev Dis. 2022;9(12):409.PubMedPubMedCentral
2.
Davies MJ, Fulton WF, Robertson WB. The relation of coronary thrombosis to ischemic myocardial necrosis. J Pathol. 1979;127(2):99–110.PubMedCrossRef
3.
Tam CC, Tse HF. Antiplatelet therapy aims and strategies in Asian patients with acute coronary syndrome or stable coronary artery disease. J Clin Med. 2022;11(24):7440.PubMedPubMedCentralCrossRef
4.
Sun Y, Liu X, Guo L, et al. HTUPA as a new thrombolytic agent for acute myocardial infarction: a multicenter, randomized study. Int J Cardiol. 2014;172(2):326–31.PubMedCrossRef
5.
6.
7.
8.
9.
Teng T, Kong CY, Huang R, et al. Mapping current research and identifying hotspots of ferroptosis in cardiovascular diseases. Front Cardiovasc Med. 2022;9:1046377.PubMedPubMedCentralCrossRef
10.
Liu T, Shu J, Liu Y, et al. Atorvastatin attenuates ferroptosis-dependent myocardial injury and inflammation following coronary microembolization via the Hif1a/Ptgs2 pathway. Front Pharmacol. 2022;13:1057583.PubMedPubMedCentralCrossRef
11.
Park TJ, Park JH, Lee GS, et al. Quantitative proteomic analyses reveal that GPX4 downregulation during myocardial infarction contributes to ferroptosis in cardiomyocytes. Cell Death Dis. 2019;10(11):835.PubMedPubMedCentralCrossRef
12.
Marinescu MC, Lazar AL, Marta MM, Cozma A, Catana CS. Non-coding RNAs: prevention, diagnosis, and treatment in myocardial ischemia-reperfusion injury. Int J Mol Sci. 2022;23(5):2728.PubMedPubMedCentralCrossRef
13.
Zhang S, Li Y, Xin S, et al. Insight into LncRNA- and CircRNA-mediated CeRNAs: regulatory network and implications in nasopharyngeal carcinoma-a narrative literature review. Cancers (Basel). 2022;14(19):4564.PubMedCrossRef
14.
Almaghrbi H, Giordo R, Pintus G, Zayed H. Non-coding RNAs as biomarkers of myocardial infarction. Clin Chim Acta. 2023;540:117222.PubMedCrossRef
15.
Su Q, Liu Y, Lv XW, Dai RX, Yang XH, Kong BH. LncRNA TUG1 mediates ischemic myocardial injury by targeting miR-132-3p/HDAC3 axis. Am J Physiol Heart Circ Physiol. 2020;318(3):H729.
16.
Kologrivova I, Shtatolkina M, Suslova T, Ryabov V. Cells of the immune system in cardiac remodeling: main players in resolution of inflammation and repair after myocardial infarction. Front Immunol. 2021;12:664457.PubMedPubMedCentralCrossRef
17.
Zhou Q, Zhang G, Liu Z, Zhang J, Shi R. Identification and exploration of novel M2 macrophage-related biomarkers in the development of acute myocardial infarction. Front Cardiovasc Med. 2022;9:974353.PubMedPubMedCentralCrossRef
18.
Qian J, Gao Y, Lai Y, et al. Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Acute Myocardial Infarction. Front Immunol. 2022;13:908815.PubMedPubMedCentralCrossRef
19.
Barrera MJ, Aguilera S, Castro I, et al. Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sjögren’s syndrome. Autoimmun Rev. 2021;20(8):102867.PubMedCrossRef
20.
Liang JY, Wang DS, Lin HC, et al. A Novel Ferroptosis-related Gene Signature for Overall Survival Prediction in Patients with Hepatocellular Carcinoma. Int J Biol Sci. 2020;16(13):2430–41.PubMedPubMedCentralCrossRef
21.
Li H, Ge Y, Fei G, Wang Z, Wang S, Wei P. Development and validation of a combined ferroptosis and immune prognostic signature for lung adenocarcinoma. Transl Cancer Res. 2022;11(10):3620–33.PubMedPubMedCentralCrossRef
22.
Zhuo S, Chen Z, Yang Y, Zhang J, Tang J, Yang K. Clinical and Biological Significances of a Ferroptosis-Related Gene Signature in Glioma. Front Oncol. 2020;10:590861.PubMedPubMedCentralCrossRef
23.
Wang J, Zhuo Z, Wang Y, et al. Identification and validation of a prognostic risk-scoring model based on ferroptosis-associated cluster in acute myeloid leukemia. Front Cell Dev Biol. 2022;9:800267.ADSPubMedPubMedCentralCrossRef
24.
Le T, Aronow RA, Kirshtein A, Shahriyari L. A review of digital cytometry methods: estimating the relative abundance of cell types in a bulk of cells. Brief Bioinform. 2021;22(4):bbaa219.PubMedCrossRef
25.
26.
Zhou Q, Liu X, Lv M, Sun E, Lu X, Lu C. Genes that predict poor prognosis in breast cancer via bioinformatical analysis. Biomed Res Int. 2021;2021:6649660.PubMedPubMedCentralCrossRef
27.
28.
Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.PubMedPubMedCentralCrossRef
29.
Szklarczyk D, Kirsch R, Koutrouli M, et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023;51(D1):D638–46.PubMedCrossRef
30.
Li J, Sun G, Ma H, et al. Identification of immune-related hub genes and miRNA-mRNA pairs involved in immune infiltration in human septic cardiomyopathy by bioinformatics analysis. Front Cardiovasc Med. 2022;9:971543.PubMedPubMedCentralCrossRef
31.
Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8 Suppl 4(Supp 4):11.ADSCrossRef
32.
Li J, Li C, Zhao Y, et al. Integrated bioinformatics analysis for novel miRNAs markers and ceRNA network in diabetic retinopathy. Front Genet. 2022;13:874885.PubMedPubMedCentralCrossRef
33.
Li J, Ma H, Wu X, et al. Promising roles of non-exosomal and exosomal non-coding RNAs in the regulatory mechanism and as diagnostic biomarkers in myocardial infarction. J Zhejiang Univ Sci B. 2023;24(4):281–300.PubMedCrossRef
34.
Li J, Wu X, Ma H, et al. New developments in non-exosomal and exosomal ncRNAs in coronary artery disease. Epigenomics. 2022;14(21):1355–72.PubMedCrossRef
35.
Zhou D, Liu X, Wang X, et al. A prognostic nomogram based on LASSO Cox regression in patients with alpha-fetoprotein-negative hepatocellular carcinoma following non-surgical therapy. BMC Cancer. 2021;21(1):246.PubMedPubMedCentralCrossRef
36.
Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143(1):29–36.PubMedCrossRef
37.
Yang L, Yu Y, Tian G, et al. H3K9ac modification was involved in doxorubicin induced apoptosis by regulating Pik3ca transcription in H9C2 cells. Life Sci. 2022;284:119107.CrossRef
38.
Cao S, Liu H, Fan J, et al. An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development. Front Immunol. 2021;12:765382.PubMedPubMedCentralCrossRef
39.
Zhang J, Huang X, Wang X, et al. Identification of potential crucial genes in atrial fibrillation: a bioinformatic analysis. BMC Med Genomics. 2020;13(1):104.PubMedPubMedCentralCrossRef
40.
Jiao K, Su P, Feng Y, Li C. Bioinformatics analysis and identification of hub genes associated with female acute myocardial infarction patients by using weighted gene co-expression networks. Medicine (Baltimore). 2023;102(17):e33634.PubMedCrossRef
41.
Xia H, Chen Y, Chen Q, Wu Y. Identification of Hypoxia-related Genes in Acute Myocardial Infarction using Bioinformatics Analysis. Comb Chem High Throughput Screen. 2023;26(4):728–42.PubMedCrossRef
42.
Chen D, Geng Y, Deng Z, et al. Inhibition of TLR4 alleviates heat stroke-induced cardiomyocyte injury by down-regulating inflammation and Ferroptosis. Molecules. 2023;28(5):2297.PubMedPubMedCentralCrossRef
43.
Chen X, Xu S, Zhao C, Liu B. Role of TLR4/NADPH oxidase 4 pathway in promoting cell death through autophagy and ferroptosis during heart failure. Biochem Biophys Res Commun. 2019;516(1):37–43.PubMedCrossRef
44.
Li H, Yang H, Wang D, Zhang L, Ma T. Peroxiredoxin2 (Prdx2) Reduces Oxidative Stress and Apoptosis of Myocardial Cells Induced by Acute Myocardial Infarction by Inhibiting the TLR4/Nuclear Factor kappa B (NF-κB) Signaling Pathway. Med Sci Monit. 2020;26:e926281.PubMedPubMedCentralCrossRef
45.
Volinia S, Hiles I, Ormondroyd E, et al. Molecular cloning, cDNA sequence, and chromosomal localization of the human phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene. Genomics. 1994;24(3):472–7.PubMedCrossRef
46.
Zeng F, Ye L, Zhou Q, et al. Inhibiting SCD expression by IGF1R during lorlatinib therapy sensitizes melanoma to ferroptosis. Redox Biol. 2023;61:102653.PubMedPubMedCentralCrossRef
47.
Cheng Q, Chen M, Liu M, et al. Correction: Semaphorin 5A suppresses ferroptosis through activation of PI3K-AKT-mTOR signaling in rheumatoid arthritis. Cell Death Dis. 2023;14(3):196.PubMedPubMedCentralCrossRef
48.
Wang Y, Shen Z, Zhao S, et al. Sipeimine ameliorates PM2.5-induced lung injury by inhibiting ferroptosis via the PI3K/Akt/Nrf2 pathway: A network pharmacology approach. Ecotoxicol Environ Saf. 2022;239:113615.PubMedCrossRef
49.
Tong Z, Li G, Su C, et al. L-Borneol 7-O-[β-D-Apiofuranosyl-(1→6)]-β-D-glucopyranoside alleviates myocardial ischemia-reperfusion injury in rats and hypoxic/reoxygenated injured myocardial cells via regulating the PI3K/AKT/mTOR signaling pathway. J Immunol Res. 2022;2022:5758303.PubMedPubMedCentralCrossRef
50.
Tai H, Tong YJ, Yu R, et al. A possible new activator of PI3K-Huayu Qutan Recipe alleviates mitochondrial apoptosis in obesity rats with acute myocardial infarction. J Cell Mol Med. 2022;26(12):3423–45.PubMedPubMedCentralCrossRef
51.
Li J, Wu X, Li C, et al. Identification and Validation of Immune-Related Biomarker Gene and Construction of ceRNA Networks in Septic Cardiomyopathy. Front Cell Infect Microbiol. 2022;12:912492.PubMedPubMedCentralCrossRef
52.
Wu Z, Liu Y, Wei L, Han M. LncRNA OIP5-AS1 Promotes Breast Cancer Progression by Regulating miR-216a-5p/GLO1. J Surg Res. 2021;257:501–10.PubMedCrossRef
53.
Zhang H, Ma J, Liu F, Zhang J. Long non-coding RNA XIST promotes the proliferation of cardiac fibroblasts and the accumulation of extracellular matrix by sponging microRNA-155-5p. Exp Ther Med. 2021;21(5):477.PubMedPubMedCentralCrossRef
54.
55.
Luo X, Gong HB, Gao HY, et al. Oxygenated phosphatidylethanolamine navigates phagocytosis of ferroptotic cells by interacting with TLR2. Cell Death Differ. 2021;28(6):1971–89.PubMedPubMedCentralCrossRef
56.
Wang D, Li X, Jiao D, et al. LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia. J Hematol Oncol. 2023;16(1):30.PubMedPubMedCentralCrossRef
57.
Peet C, Ivetic A, Bromage DI, Shah AM. Cardiac monocytes and macrophages after myocardial infarction. Cardiovasc Res. 2020;116(6):1101–12.PubMedCrossRef
Metadata
Title
Integrated analysis and validation of ferroptosis-related genes and immune infiltration in acute myocardial infarction
Authors
Xinyu Wu
Jingru Li
Shengjie Chai
Chaguo Li
Si Lu
Suli Bao
Shuai Yu
Hao Guo
Jie He
Yunzhu Peng
Huang Sun
Luqiao Wang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2024
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-023-03622-z

Other articles of this Issue 1/2024

BMC Cardiovascular Disorders 1/2024 Go to the issue

Research

Association of parathyroid hormone with risk of hypertension and type 2 diabetes: a dose-response meta-analysis

Research

Safe and promising outcomes of in-hospital preoperative rehabilitation for coronary artery bypass grafting after an acute coronary syndrome

Research

Prevalence and modifiable risk factors of cognitive frailty in patients with chronic heart failure in China: a cross-sectional study

Research

The safety and efficacy of nonvitamin K antagonist oral anticoagulants in morbidly obese patients with atrial fibrillation: a meta-analysis

Research

Effect of inflammation on association between cancer and coronary artery disease

Research

Triglyceride glucose-body mass index as a novel predictor of slow coronary flow phenomenon in patients with ischemia and nonobstructive coronary arteries (INOCA)

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits