Serum Hepatocyte-Derived Fibrinogen-Related Protein-1: A Novel Biomarker for Severity and Clinical Outcome in Acute Ischemic Stroke

This work was designed to investigate the expression of hepatocyte-derived fibrinogen-related protein-1 (HFREP1) and its clinical value in patients with first-ever acute ischemic stroke (AIS).

A total of 222 newly diagnosed patients with first-onset AIS admitted to the Encephalopathy Center of Jiangsu Province Hospital of Chinese Medicine from April 2023 and September 2024 were enrolled as the AIS group. Besides, 89 healthy individuals matched for age and sex were included in the control cohort. Baseline demographic characteristics and laboratory indicators were gathered from all enrolled subjects. Serum HFREP1 levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. Spearman correlation analysis was adopted to analyze the correlation between HFREP1 expression and other laboratory indexes. Logistic regression was applied to identify independent factors affecting the severity and short-term prognosis of AIS. Receiver operating characteristic (ROC) curve analysis was further performed to assess the predictive efficacy of serum HFREP1 for AIS severity and short-term clinical outcome.

Compared with the control group, the AIS group presented obviously higher serum HFREP1 concentrations (P<0.001). Moreover, HFREP1 levels were notably increased in patients with moderate-to-severe stroke (P<0.001) and those with poor short-term prognosis (P<0.05). Elevated serum HFREP1 levels were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores (r_s=0.22, P=0.001), neutrophil count (r_s=0.17, P<0.01), and neutrophil-to-lymphocyte ratio (NLR) (r_s=0.22, P<0.01). Univariate analysis indicated that elevated HFREP1 levels were significantly associated with severe stroke and adverse short-term prognosis. After multivariate confounding adjustment, HFREP1 levels remained independently correlated with severe stroke in Model 4 [odds ratio (OR)=1.004, 95% confidence interval (CI):1.000-1.008, P=0.039] and unfavorable short-term prognosis in Model 2 (OR=1.004, 95% CI:1.000-1.007, P=0.041). ROC curve analysis revealed that HFREP1 exhibited a favorable predictive performance for stroke severity [area under the curve (AUC)=0.665, 95% CI:0.573-0.756, P<0.01] and short-term prognosis (AUC=0.617, 95% CI:0.503-0.732, P<0.05). Overall, the optimal cut-off value of HFREP1 was 35.35 ng/mL for identifying AIS, and 68.45 ng/mL for evaluating stroke severity and predicting adverse prognosis.

Elevated serum HFREP1 level might act as a novel and promising early biomarker for evaluating disease severity and predicting poor short-term prognosis in patients with first-onset AIS.