Serum Sestrin2 Emerges as a Prognostic Biomarker of Human Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Cohort Single-Center Study

Background: Sestrin2 functions as a neuroprotective factor. Herein, serum sestrin2 was investigated with respect to its associations with severity, delayed cerebral ischemia (DCI) and prognosis of aneurysmal subarachnoid hemorrhage (aSAH). Methods: In this prospective, observational, cohort, single-center study, serum sestrin2 levels were measured at entry into the study in 45 healthy controls and at admission in 135 aSAH patients. Also, they were gauged in other time points (namely, at days 1, 2, 3, 5 and 7) among 45 patients. Unfavorable prognosis was defined as extended Glasgow Outcome Scale (GOSE) scores of 1-4 at six months after aSAH. Results: Serum sestrin2 levels were immediately raised at admission in patients, increased thereafter, peaked at day 2, declined afterwards till day 7, and were significantly higher than those in controls (all P<0.001). Serum sestrin2 levels had independent correlation with Hunt-Hess scores (beta, 1.715; 95% confidence interval (CI), 0.595-2.835; P=0.003) and modified Fisher scores (beta, 2.505; 95% CI, 1.102-3.907; P=0.001). Alternatively, serum sestrin2 levels, which were independently correlated with 6-month GOSE scores (beta, -0.050; 95% CI, -0.099-0.001; P=0.044), were independently associated with DCI (odds ratio, 1.079; 95% CI, 1.008- 1.156; P=0.029) and unfavorable prognosis (odds ratio, 1.093; 95% CI, 1.020-1.172; P=0.012). DCI and prognosis prediction models, which were composed of serum sestrin2, Hunt-Hess scores and modified Fisher scores, were comparatively stable and clinically beneficial under calibration curve and decision curve. Prognosis prediction model showed significantly higher area under receiver operating characteristic curve than serum sestrin2, Hunt-Hess scores and modified Fisher scores alone (all P<0.05). Conclusion: A significant enhancement of serum sestrin2 levels after aSAH is independently related to severity, DCI and poor prognosis following aSAH. The models incorporating serum sestrin2 perform well in predicting the DCI and prognosis of aSAH patients. Presumably, determination of serum sestrin2 may be of clinical significance in aSAH.