Identification of annexin A10 as a candidate serum biomarker associated with neurological outcome after cardiac arrest

Accurate early neurological prognostication following cardiac arrest remains a major clinical challenge because of post-resuscitation brain injury. Although biomarkers such as neuron-specific enolase (NSE) and neurofilament light chain (NfL) are widely investigated, limitations in their clinical application remain. This study employed high-throughput proteomics to identify and evaluate annexin A10 (ANXA10) as an exploratory serum biomarker associated with neurological outcomes after cardiac arrest. We conducted a two-stage exploratory study. The discovery phase ( N = 50) included 34 post-resuscitation patients together with patients with acute ischemic stroke and healthy controls. Serum samples were analyzed using the Olink proteomics platform, and candidate biomarkers were identified through differential proteomic analysis and machine learning-based feature selection. Candidate proteins were subsequently evaluated in an independent ELISA validation cohort ( N = 120), including 70 post-resuscitation patients. Neurological outcomes were assessed at hospital discharge using the Cerebral Performance Category (CPC) scale, with CPC 3–5 defined as poor neurological outcomes (PNO). In the validation cohort (7 good neurological outcomes vs. 63 poor neurological outcomes), serum ANXA10 concentrations were significantly higher in the PNO group than in the GNO group (median, 417.73 vs. 140.66 pg/mL; P = 0.002). ANXA10 showed a moderate positive correlation with CPC score ( r = 0.417, P < 0.001). In this exploratory cohort, ANXA10 demonstrated an area under the receiver operating characteristic curve (AUC) of 0.838 (95% CI 0.588–1.000) for predicting poor neurological outcomes. DeLong’s test showed no statistically significant difference between the AUC of ANXA10 and those of the evaluated 3-protein panel (NSE, NfL, and Tau; AUC = 0.839, P = 0.980) or 5-protein panel (AUC = 0.860, P = 0.869). These findings should be interpreted cautiously because of the exploratory study design, limited sample size, and wide confidence intervals. ANXA10 is an exploratory candidate biomarker associated with neurological outcomes after cardiac arrest. Although its observed discriminatory performance was comparable to that of the evaluated multiprotein panels in this exploratory cohort, substantial uncertainty remains because of the highly imbalanced sample size and wide confidence intervals. Larger prospective studies are required to validate these findings and determine whether ANXA10 provides independent prognostic value beyond established clinical and biochemical predictors.