Key result
Transcriptomic analysis identifies 7 macrophage- and ferroptosis-related candidate genes altered in myocardial infarction.
Why the study?
Macrophage-mediated inflammation and ferroptosis-related stress responses are implicated in MI, but transcriptomic identification of macrophage- and ferroptosis-related candidate genes requires rigorous control of false-positive findings.
The identification of seven macrophage- and ferroptosis-related genes provides candidate biomarkers and potential mechanistic insights into immune infiltration and inflammatory responses following myocardial infarction.
Answers are grounded in this paper and cite their sources.
These genes merit exploration as MI biomarkers; hypothesis-generating for macrophage-ferroptosis links and requires prospective validation.
Globally, myocardial infarction (MI) remains a major cause of morbidity and mortality. Macrophage-mediated inflammation and ferroptosis-related stress responses have both been implicated in MI; however, transcriptomic identification of macrophage- and ferroptosis-related candidate genes requires rigorous control of false-positive findings. In this revised study, two peripheral blood transcriptomic datasets, GSE29532 and GSE48060, were integrated after probe annotation, independent normalization, merging based on common genes, and ComBat batch correction. Batch-correction quality was evaluated using both visualization and quantitative metrics. Differential expression analysis was performed using the limma package with adj.P.Val < 0.05 as the primary threshold. A total of 213 differentially expressed genes were identified, including 101 upregulated and 112 downregulated genes. Intersecting FDR-supported DEGs with macrophage-related and ferroptosis-related gene sets identified seven primary MFRDEGs: SMAD7, MMD, PTPN6, DDIT3, AKR1C3, PHF21A, and ACSL1. GO enrichment analysis was interpreted as exploratory functional annotation because of the small input gene set, whereas whole-ranked-gene GSEA highlighted TNFA/NF-kB inflammatory signaling, complement-related innate immune signaling, and reactive oxygen species-related transcriptional programs. Because the revised PPI analysis did not produce reliable interactions among the seven primary MFRDEGs, candidate gene prioritization was performed instead of defining interaction-derived hub genes. ssGSEA suggested a robust neutrophil-related alteration in MI, while macrophage- and monocyte-related signatures showed trend-level changes after FDR correction. Exploratory ROC analysis was performed for selected candidate genes. RT-qPCR validation further showed that SMAD7, PTPN6, DDIT3, PHF21A, and ACSL1 were increased, whereas MMD and AKR1C3 were decreased in AMI peripheral blood samples, consistent with the transcriptomic results. These findings provide FDR-supported candidate-level evidence linking macrophage- and ferroptosis-related transcriptional alterations to immune signatures in MI and warrant further validation in larger cohorts and mechanistic studies.
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Wang et al. (2026) studied Myocardial infarction (n=119). Myocardial infarction vs. Normal controls was evaluated on Differentially expressed macrophage- and ferroptosis-related genes (MFRDEGs) (p=<0.05). Transcriptomic analysis and RT-qPCR validation identified seven macrophage- and ferroptosis-related candidate genes (SMAD7, MMD, PTPN6, DDIT3, AKR1C3, PHF21A, and ACSL1) significantly altered in myocardial infarction.
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