Proteomics-Based Serum Alterations of the Human Protein Expression after Out-of-Hospital Cardiac Arrest: Pilot Study for Prognostication of Survivors vs. Non-Survivors at Day 1 after Return of Spontaneous Circulation (ROSC)

Abstract

Background: Targeted temperature management (TTM) is considered standard therapy for patients after out-of-hospital cardiac arrest (OHCA), cardiopulmonary resuscitation (CPR), and return of spontaneous circulation (ROSC). To date, valid protein markers do not exist to prognosticate survivors and non-survivors before the end of TTM. The aim of this study is to identify specific protein patterns/arrays, which are useful for prediction in the very early phase after ROSC. Material and Methods: A total of 20 adult patients with ROSC (19 male, 1 female; 69.9 ± 9.5 years) were included and dichotomized in two groups (survivors and non-survivors at day 30). Serum samples were drawn at day 1 after ROSC (during TTM). Three panels (organ failure, metabolic, neurology, inflammation; OLINK, Uppsala, Sweden) were utilised. A total of four proteins were found to be differentially regulated (>2- or t-test). Bioinformatic platforms were utilised to analyse pathways and identify signalling cascades and to screen for potential biomarkers. Results: A total of 276 proteins were analysed and revealed only 11 statistically significant protein alterations (Siglec-9, LAYN, SKR3, JAM-B, N2DL-2, TNF-B, BAMBI, NUCB2, STX8, PTK7, and PVLAB). Following the Bonferroni correction, no proteins were found to be regulated as statistically significant. Concerning the protein fold change for clinical significance, four proteins (IL-1 alpha, N-CDase, IL5, CRH) were found to be regulated in a clinically relevant context. Conclusions: Early analysis at 1 day after ROSC was not sufficiently possible during TTM to prognosticate survival or non-survival after OHCA. Future studies should evaluate protein expression later in the course after ROSC to identify promising protein candidates.

Keywords

• proteomics
• CPR
• protein expression
• targeted temperature management
• ROSC