Proteomic Investigation of Serum Biomarkers for Early Neurological Prognosis in Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation: A Prospective Multi-Center Pilot Study

초록

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising intervention for refractory cardiac arrest; however, predicting neurological outcomes remains challenging. This study aimed to identify early prognostic biomarkers for neurological outcomes in ECPR patients using comprehensive proteomic profiling. Methods: In this multi-center prospective cohort study, serum samples were collected at 0, 24, 48, and 72 hours after ECPR and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Among 1,135 quantified proteins, differential expression was defined by |log2fold-change| ≥ 1 and P< 0.05. Twenty-two patients were enrolled and stratified by 90-day Cerebral Performance Category (CPC) scores: good neurological outcome (CPC score 1–2, n = 15) and poor neurological outcome (CPC score 3–5, n = 7). Results: Proteomic analysis suggested distinct temporal expression patterns and potential differences in key proteins between neurological outcome groups. Four proteins associated with neuronal function or neuroinflammation, including GRN (24 hours), S100A6 (0 hours), PRDX6 (48 hours), and PTPRF (24 hours, 48 hours), showed numerically greater discriminative performance than neuron-specific enolase (NSE). Their areas under the receiver operating characteristic curve were 0.857, 0.833, 0.821, and 0.821, respectively, compared with 0.800 for NSE at 48 hours. Conclusion: In this preliminary study, GRN, S100A6, PRDX6, and PTPRF exhibited improved discriminative performance compared with NSE, suggesting their potential as promising serum proteomic biomarkers for early neuroprognostication after ECPR. While these exploratory findings warrant validation in larger cohorts, they establish a compelling foundation for the development of next-generation, biomarker-based models to guide clinical management in ECPR patients. © 2026 The Korean Academy of Medical Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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