Unbiased metabolomics screening for potential biomarkers in patients with In-stent restenosis post percutaneous coronary intervention

<i>Purpose.</i> This study utilizes untargeted metabolomics to identify novel serum biomarkers and metabolic pathways linked to in-stent restenosis (ISR). <i>Methods.</i> This retrospective study included patients who underwent percutaneous coronary intervention (PCI) at the Chinese PLA General Hospital between February 2018 and December 2018. Serum metabolites were analyzed using gas chromatography-mass spectrometry (GC-MS). Multivariate analysis was used to identify differential metabolites, and pathway enrichment analysis was performed to explore their biological significance. <i>Results.</i> A total of 61 patients were enrolled, comprising 18 in the ISR group and 43 in the non-ISR group. The ISR group demonstrated a higher prevalence of smoking (50% vs. 21%, <i>p</i> = 0.023), a greater incidence of previous myocardial infarction (72% vs. 37%, <i>p</i> = 0.004), and a lower left ventricular ejection fraction (51% vs. 58%, <i>p</i> = 0.004) compared to the non-ISR group. Seven differential metabolites were identified, with five being upregulated (inosine, myo-inositol, 3-cyanoalanine, monostearin, and glutamine) and two downregulated (biuret and 3-methylcatechol). Pathway enrichment analysis revealed three major metabolic pathways associated with ISR: inositol phosphate metabolism, alanine-aspartate-glutamate metabolism, and the phosphatidylinositol signaling system. Receiver operating characteristic (ROC) analysis indicated that inosine had the highest diagnostic performance [The area under the curve (AUC) = 0.807], followed by myo-inositol (AUC = 0.705) and monostearin (AUC = 0.643). The combined biomarker panel significantly enhanced diagnostic accuracy, achieving an AUC of 0.925, indicating strong predictive potential for ISR. <i>Conclusions.</i> This study identified seven potential serum biomarkers and three metabolic pathways linked to ISR. These findings enhance our understanding of the metabolic mechanisms underlying ISR and could aid in the development of non-invasive diagnostic tools and therapeutic strategies.