Concentrations of glial fibrillary acidic protein in the blood serum of patients with glioblastoma of the brain

Introduction. Glioblastoma is one of the most aggressive malignant brain tumors. In a number of observations, these tumors are not sensitive to drug therapy, are often prone to recurrence, and the prognosis for most patients remains unfavorable. Therefore, one of the promising directions is the search for biomarkers for timely diagnosis and monitoring of the disease.

Aim. To analyze the content of the soluble form of the GFAP protein in the blood serum of patients with glioblastoma and determine its prognostic significance.

Material and methods. We examined 178 patients (99 men and 79 women) with glioblastoma of the brain aged from 18 to 82 years, who underwent examination and treatment at the Federal State Budgetary Institution "National Medical Research Center of Oncology named after. N.N. Blokhin" in the period from 2016 to 2023. All of them were diagnosed with glioblastoma (IV degree of malignancy), which was confirmed by morphological and molecular genetic studies. The control group consisted of 34 healthy donors (18 men and 16 women) aged from 19 to 80 years and the comparison group of 31 patients (26 men and 5 women) with traumatic brain injuries of varying severity aged 19 to 56 years. GFAP concentrations were determined in blood serum samples from patients with glioblastoma before treatment, and in patients with traumatic brain injuries 2-3 hours after injury using enzyme immunoassay "Human test system GFAP ELISA" (Biovendor, Czech Republic). Data were processed using Statistica 10 (StatSoft) and SPSS (IBM) software. When comparing indicators and analyzing their relationships, the nonparametric Kruskal–Wallis test was used. Analysis of the information content of the diagnostic method by assessing its sensitivity and specificity was carried out by constructing ROC curves and calculating the area under them (AUC). Overall survival analysis was performed using the Kaplan–Meier method. Comparison of the statistical significance of differences between indicators was carried out using the log-rank test. Differences and correlations were considered statistically significant at p < 0.05.

Results. In the blood serum of healthy donors, GFAP was detected only in 8.8% (3 out of 34) of those examined, and its median content was 0 ng/ml. In patients with glioblastoma, GFAP was detected in 73.6% of cases (131 out of 178 patients) and its median content was 0.196 ng/ml. Slightly less frequently (in 20 of 31 patients, 64.5%), GFAP was found in patients with traumatic brain injuries and its median content was 0.027 ng/ml. ROC analysis showed that for the group of patients with glioblastoma, the area under the ROC curve was 0.855 (p = 0.0001), for patients with traumatic brain injury – 0.793 (p < 0.0001). The analysis showed that high levels of GFAP more than 0.014 ng/ml in the blood serum of patients with glioblastoma are prognostically unfavorable, although they did not reach statistical significance (p = 0.4). The median survival of patients was 26.6 months with GFAP levels < 0.014 ng/ml, while in patients with higher levels of this protein (≥0.014 ng/ml) the median survival was 14 months.

Conclusions. GFAP was detected in the blood serum of 73.6% of patients with glioblastoma of the brain, 64.5% of patients with traumatic brain injury, and only 8.8% of healthy donors. GFAP concentrations in patients with glioblastoma and patients with traumatic brain injury did not differ from each other, but were significantly higher compared to the control group. GFAP levels in the blood serum of patients with glioblastoma ≥ 0.014 ng/ml are associated with an unfavorable prognosis of overall survival.