Annexin A10 as a novel serum biomarker for early neurological prognostication after cardiac arrest

Background Accurate early neurological prognostication after cardiac arrest remains challenging. Established serum biomarkers such as neuron-specific enolase (NSE) and neurofilament light chain (NfL) have important limitations, and additional complementary biomarkers are needed to improve risk stratification after return of spontaneous circulation (ROSC). Methods In this exploratory discovery and validation study, high-throughput serum proteomic profiling using a neurology-focused panel was performed in patients after cardiopulmonary resuscitation, with acute ischemic stroke patients and healthy individuals as controls. Differential expression analysis combined with multiple machine-learning approaches was used for biomarker selection. Candidate proteins were validated using enzyme-linked immunosorbent assay (ELISA) in an independent ROSC cohort. Neurological outcome at hospital discharge was assessed using the Cerebral Performance Category (CPC) scale. Results Among 384 proteins screened, annexin A10 (ANXA10) was consistently identified as strongly associated with poor neurological outcome (CPC 3–5). In the validation cohort, serum ANXA10 levels were significantly higher in patients with unfavorable outcomes. ANXA10 demonstrated the highest discriminative performance (AUC 0.838) compared with NSE and NfL. A combined model incorporating ANXA10, NSE, and NfL further improved prognostic performance. Conclusion ANXA10 is a novel serum biomarker strongly associated with neurological outcome after cardiac arrest and provides complementary prognostic value beyond established neuronal injury markers. Integration of ANXA10 into multimodal prognostic assessment may improve early neurological risk stratification after ROSC.