# Serial assessment of the novel biomarker MFGE8 in comparison with GFAP for predicting severity and outcome after traumatic brain injury

## TL;DR

This study compares the usefulness of two biomarkers, MFGE8 and GFAP, in predicting the severity and outcomes of traumatic brain injury.

## Contribution

The study introduces MFGE8 as a novel biomarker with strong early prognostic value for traumatic brain injury.

## Key findings

- MFGE8 levels peak 24 hours post-injury and correlate strongly with clinical and radiological severity.
- MFGE8 shows superior prognostic performance for 30-day mortality compared to GFAP at 24 hours post-injury.
- Both biomarkers are elevated in patients with unfavorable outcomes and death compared to survivors.

## Abstract

Early assessment of traumatic brain injury (TBI) severity and prognosis is critical for clinical diagnosis and treatment. However, existing biomarkers have limitations in terms of predictive accuracy and timeliness. This study aimed to investigate the dynamic changes of the novel biomarker milk fat globule-EGF factor 8 (MFGE8) following TBI and systematically evaluate its value in predicting TBI severity and clinical prognosis, in comparison to GFAP.

This was a prospective, single-center observational study involving 70 patients with acute TBI and 33 healthy controls. Serum levels of MFGE8 and GFAP were quantitatively determined by ELISA at admission (within 12 h of injury) and at 24, 48, and 72 h after injury. TBI severity was graded by the Glasgow Coma Scale (GCS) at admission, and the Rotterdam CT score was used to evaluate radiological injury severity. Outcome measures included 30-day mortality and the Glasgow Outcome Scale-Extended (GOSE) score at 3 months. Longitudinal biomarker trajectories and their associations with clinical severity, radiological severity, and outcomes were analyzed using linear mixed-effects models (LMMs), with Spearman’s correlation and receiver operating characteristic (ROC) analyses performed as complementary assessments.

The levels of serum MFGE8 and GFAP in TBI patients at all time points were significantly higher than those in the control group (p < 0.001) and peaked 24 h post-injury. In addition, significant correlations were shown between the two biomarkers, as well as between each biomarker and the clinical and radiographic severity scores (all p < 0.001). LMMs demonstrated significant differences in biomarker concentrations across clinical severity, radiological severity, and outcome groups, with significant main effects of time and group and significant group × time interactions. Pairwise comparisons indicated that GFAP provided earlier separation of clinical severity at admission, whereas MFGE8 exhibited its strongest severity separation at 24 h post-injury, with similar time-dependent patterns observed for radiological severity. Both biomarkers were consistently higher in patients with unfavorable outcomes and death compared with favorable survivors at admission and 24 h post-injury. MFGE8 showed superior prognostic performance for 30-day mortality at 24 h (AUC = 0.895), while GFAP demonstrated strong early discriminatory ability at admission. The GFAP/MFGE8 ratio exhibited moderate prognostic value.

Serum MFGE8 is a promising biomarker after TBI. It is closely related to the injury severity and clinical prognosis. Particularly, it demonstrates high prognostic predictive value within 24 h post-injury. Continuous monitoring of MFGE8 may aid in early risk stratification and prognostic assessment for TBI.