Potential diagnostic biomarkers: 6 cuproptosis- and ferroptosis-related genes linking immune infiltration in acute myocardial infarction

Abstract

The current diagnostic biomarkers of acute myocardial infarction (AMI), troponins, lack specificity and exist as false positives in other non-cardiac diseases. Previous studies revealed that cuproptosis, ferroptosis, and immune infiltration are all involved in the development of AMI. We hypothesize that combining the analysis of cuproptosis, ferroptosis, and immune infiltration in AMI will help identify more precise diagnostic biomarkers. The results showed that a total of 19 cuproptosis- and ferroptosis-related genes (CFRGs) were differentially expressed between the healthy and AMI groups. Functional enrichment analysis showed that the differential CFRGs were mostly enriched in biological processes related to oxidative stress and the inflammatory response. The immune infiltration status analyzed by ssGSEA found elevated levels of macrophages, neutrophils, and CCR in AMI. Then, we screened 6 immune-related CFRGs (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4, STAT3) to construct a nomogram for predicting AMI and validated it in the GSE109048 dataset. Moreover, we also identified 5 pivotal miRNAs and 10 candidate drugs that target the 6 feature genes. Finally, RT-qPCR analysis verified that all 6 feature genes were upregulated in both animals and patients. In conclusion, our study reveals the significance of immune-related CFRGs in AMI and provides new insights for AMI diagnosis and treatment.

Comprehensive bioinformatics analysis reveals the role of cuproptosis-related gene Ube2d3 in myocardial infarction

“…Mengdan Miao et al. have confirmed the role of six cuproptosis- and ferroptosis-related genes (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4 and STAT3) in predicting the progression of AMI ( 20 ). Additionally, Zheng Liu et al.…”

“…Consequently, we hypothesize that Ube2d3 may induce cuproptosis to affect the development of MI. Mengdan Miao et al have confirmed the role of six cuproptosis-and ferroptosis-related genes (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4 and STAT3) in predicting the progression of AMI (20). Additionally, Zheng Liu et al identified CRG GLS as a diagnostic gene for AMI (21).…”

Identification of mitochondria-related gene biomarkers associated with immune infiltration in acute myocardial infarction

“…Hence, it is crucial to identify novel diagnostic biomarkers to accurately predict AMI, which improves treatment efficiency and benefits patient outcomes. 13 …”

Integrative analyses and validation of ferroptosis-related genes and mechanisms associated with cerebrovascular and cardiovascular ischemic diseases

“…A recent biological information and validation study on ferroptosis-related genes (FRGs) during ischemic stroke (IS) screened hub genes related to ferroptosis and suggested a possible mechanism for dexmedetomidine-mediated inhibition of ferroptosis during IS [ 9 ], and during myocardial ischemia (MI), the same biosignature study identified genes related to ferroptosis and carried out immune infiltration analyses and confirmation of related hub genes [ 10 , 11 ], these studies separately from the direction of MI and IS to explore the role of FRGs in MI and IS, but did not further study the common characteristics of the process of cardio-cerebral ischemia, and to further clarify the process of cardio-cerebral ischemia with a consistent trend of expression of the hub genes of ferroptosis, which is precisely the problem explored in this paper, the study of the FRGs in cardio-cerebral ischemia. The study of the common role of ferroptosis genes in ischemia is of great significance in the search for common pathways and mechanisms of ischemic injury.…”