Key result
Mitochondrial metabolism-related genes PPT2 and MED21 were significantly downregulated in patients with coronary heart disease, demonstrating diagnostic capacity with AUC values >0.7.
Why the study?
Coronary heart disease affects quality of life through impaired coronary artery blood supply, prompting investigation into the molecular mechanisms of mitochondrial metabolism-related genes.
Case-Control (n=175)
PPT2 and MED21 were identified and validated as novel mitochondrial metabolism-related biomarkers that are significantly downregulated in patients with coronary heart disease.
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May support biomarker research in coronary heart disease; leaves open prospective clinical validation before any diagnostic use.
Coronary heart disease (CHD) affects life quality of patients by impaired coronary artery blood supply. We were planning to study the molecular mechanisms of mitochondrial metabolism-related genes (MMRGs) in CHD. The following data were sourced from public databases: transcriptome data of CHD and MMRGs. The candidate genes were obtained by differential expression analysis and MMRGs. The identification of biomarkers was facilitated by machine learning algorithms and gene expression analyses. Of particular significance was the utilization of the nomogram for the evaluation of the diagnostic efficacy of the biomarkers. Following this, enrichment analysis, immune infiltration analysis, compound prediction and molecular docking were performed. Expression levels of biomarkers were tested in vitro by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Palmitoyl protein thioesterase 2 (PPT2) and Mediator complex subunit21(MED21) were validated as biomarkers. A nomogram developed utilizing these biomarkers demonstrated a satisfactory capacity for differentiating among various sample types. The neuroactive ligand-receptor interaction, polycomb repressive complex, protein processing in endoplasmic reticulum, and calcium signaling pathway were the pathway co-enriched by biomarkers. Immune infiltration analysis indicated that PPT2 and MED21 were anticorrelated with regulatory T cells and central memory CD4 T cells, respectively. In addition, 20 compounds targeting PPT2 and MED21 were identified, respectively. Notably, molecular docking studies demonstrated a strong binding affinity between PPT2 and benzo(a)pyrene. The RT-qPCR analyses confirmed the downregulation of PPT2 and MED21 in CHD. PPT2 and MED21 were identified associated with mitochondrial metabolism in CHD, providing effective support for clinical diagnosis of CHD.
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Zhao et al. (2026) conducted a case-control in Coronary heart disease (n=175). PPT2 and MED21 biomarkers vs. Healthy controls was evaluated on Expression levels and diagnostic capacity (AUC) of PPT2 and MED21 (p=<0.001). Mitochondrial metabolism-related genes PPT2 and MED21 were significantly downregulated in patients with coronary heart disease, demonstrating diagnostic capacity with AUC values >0.7.
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