Serum sestrin2 as a potential prognostic biomarker for acute ischemic stroke

Sestrin2 has been reported to be associated with the occurrence of acute ischemic stroke (AIS), but its prognostic significance in patients with AIS remains unclear. This study aimed to investigate the prognostic value of serum sestrin2 in patients with AIS and to develop a prognostic model incorporating serum sestrin2. This observational study primarily comprised a retrospective prognostic cohort with an embedded exploratory cross-sectional comparison. A total of 100 patients with AIS and 47 healthy controls were enrolled. Serum sestrin2, interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels were measured using enzyme-linked immunosorbent assay. Associations between serum sestrin2 and clinical characteristics were analysed, and multivariable logistic regression was performed to identify independent predictors of unfavorable outcome, defined as a modified Rankin Scale (mRS) score > 2 at 3 months. A prognostic nomogram was developed and internally validated using bootstrap resampling. Compared with healthy controls, patients with AIS had significantly higher serum sestrin2 and IL-6 levels, although this comparison should be interpreted cautiously because of the age imbalance between groups. Among the 100 patients with AIS, 26 were classified as having an unfavorable functional outcome (mRS > 2) at 3 months. Serum sestrin2 levels were positively correlated with both IL-6 concentrations and mRS scores. After adjustment for age and major vascular risk factors, higher serum sestrin2 levels and NIHSS scores remained independently associated with unfavorable 3-month outcomes. Compared with the NIHSS-alone model, the addition of serum sestrin2 significantly improved overall model fit, although improvements in discrimination and reclassification metrics were not statistically significant. A nomogram incorporating these two variables demonstrated good discrimination (AUC 0.897, 95% CI 0.830–0.963), satisfactory calibration, and favorable performance after bootstrap internal validation. Decision curve analysis suggested potential clinical value for early risk stratification. Serum sestrin2 was independently associated with unfavorable functional outcomes in patients with AIS and may serve as a complementary prognostic biomarker. A prognostic nomogram incorporating serum sestrin2 and NIHSS score demonstrated promising predictive performance and may provide complementary information for early risk stratification after AIS. External validation is required before clinical implementation. ChiCTR2600124185 (Chinese Clinical Trial Registry, Registered 8 May 2026).