Plasma metabolomic analysis of proximal occluded artery in acute large vessel occlusion stroke with futile recanalization

To characterize the plasma metabolomic profile of proximal occluded artery in futile recanalization (FR) after endovascular treatment (EVT) for acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO). In this prospective study, plasma from the proximal occluded artery was collected from LVO-AIS patients during EVT, before mechanical thrombectomy and before recanalization. Untargeted metabolomics was performed using LC-MS/MS. Patients were divided into FR and non-FR groups based on 90-day modified Rankin Scale score. Differential metabolites were screened using VIP > 1 and P < 0.05, followed by KEGG pathway enrichment analysis. Among 40 patients (20 FR, 20 non-FR), 123 candidate differential metabolites were identified. Four key metabolites were selected: dehydroepiandrosterone, testosterone, progesterone, and stearidonic acid. In FR patients, dehydroepiandrosterone and stearidonic acid were downregulated, while testosterone and progesterone were upregulated. Pathway enrichment showed involvement of steroid hormone biosynthesis, cortisol synthesis/secretion, and aldosterone synthesis/secretion, related to immune regulation, oxidative stress, and inflammation. All four metabolites were significantly associated with FR ( P < 0.05). Their combination predicted FR with an AUC of 0.965 (95% CI: 0.918–1.000), with a sensitivity of 80.0% and specificity of 100.0% at the optimal threshold. This first systematic description of proximal occluded artery plasma metabolomics in FR reveals steroid hormone metabolism disorder as a key feature, characterized by downregulation of dehydroepiandrosterone/stearidonic acid and upregulation of testosterone/progesterone. These four metabolites are candidate biomarkers for FR.