Direct RNA sequencing identified solute carrier family 2 member 1 to improve neurological outcome prediction after cardiac arrest

Background: Cardiac arrest (CA) is a major cause of mortality and morbidity. Accurate prediction of neurological outcome and survival remains challenging. In this context, our study aimed to explore novel molecular biomarkers that could provide additional insights into the pathophysiology of brain injury after CA and potentially distinguish patients with no brain injury (CPC 1) from those with any degree of neurological damage from moderate injury up to death (CPC 2–5), and complement existing prognostic tools. Methods: Whole blood samples collected 48 h after return of spontaneous circulation were analyzed by RNA sequencing in a subgroup of 50 CA patients from the monocenter North Pole cohort, and by quantitative PCR in 233 patients from the same cohort as well as in 511 patients from the multicenter TTM trial. The association of gene expression changes with 6-month neurological outcome (assessed by the Cerebral Performance Category (CPC) score) and survival was studied. Results: In a discovery phase with a subset of 50 patients from the North Pole cohort (25 CPC 1 and 25 CPC 5), direct RNA sequencing identified the solute carrier family 2 member 1 (SLC2A1), a gene encoding a major glucose transporter at the blood–brain barrier (GLUT1), as significantly upregulated in CPC 5 patients (dead with severe neurological impairment) compared to survivors without neurological sequelae (CPC 1). This upregulation was confirmed by quantitative PCR and extended to the entire North Pole cohort (p < 0.001). SLC2A1 was an independent predictor of neurological sequelae or death in this cohort. In the TTM trial, SLC2A1 was also upregulated in patients with neurological sequelae or death (p < 0.001) and was an independent predictor of neurological sequelae or death, providing an incremental predictive value to a baseline clinical model (odds ratio = 2.06, 95% confidence interval 1.31–3.4, p = 2.82E-03, and likelihood ratio test p < 0.001). Conclusion: Blood level of SLC2A1 is a tentative blood biomarker that may aid in neurological outcome prediction after CA and also provide new insights into post-CA injury mechanisms.