Analysis of the overall survival of patients with primary glioblastoma of the brain depending on glial fibrillary acidic protein content in blood serum
- Authors: Kleimenova O.N.1, Alferov A.A.1,2, Lyubimova N.V.1,2, Mitrofanov A.А.2, Bekyashev A.K.2, Kovaleva O.V.2, Gershtein Е.S.1,2, Kushlinskii N.E.1,2, Stilidi I.S.2
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Affiliations:
- Federal State Budgetary Educational Institution of Higher Education «Russian University of Medicine» of the Ministry of Health of Russia
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
- Issue: Vol 28, No 4 (2025)
- Pages: 41-50
- Section: Medical chemistry
- URL: https://journals.eco-vector.com/1560-9596/article/view/678972
- DOI: https://doi.org/10.29296/25877313-2025-04-05
- ID: 678972
Cite item
Abstract
Introduction. Glioblastoma is one of the most aggressive malignant brain tumors characterized by low sensitivity to drug therapy, frequent recurrence after surgical removal of the tumor, and an extremely unfavorable prognosis.
Aim. To analyze the overall survival of patients with primary glioblastoma of the brain based on the glial fibrillary acidic protein (GFAP) content of in blood serum.
Material and methods. 176 patients with primary malignancy grade IV glioblastoma confirmed by morphological and molecular genetic studies (99 men and 77 women) aged 18–82 years who underwent examination and treatment at the N.N. Blokhin National Medical Research Center of Oncology in the period from 2013 to 2024 were enclosed in the study. GFAP concentration in the pre-treatment blood serum was determined by enzyme immunoassay using Human GFAP ELISA kit (Biovendor, Czech Republic). The obtained data were processed using Statistica 10 (StatSoft) and SPSS (IBM) programs. Overall survival analysis was performed using the Kaplan–Meier method with the log-rank test for comparisons. Differences were considered statistically significant at p < 0.05.
Results. 72 of 176 patients were alive at the end of the study, the median follow-up period being 7.8 months, while 104 patients with died within a period of 1 to 103 months the median survival being 9.1 months. The median lifespan of all patients with glioblastoma was 14.8 months. 1-year overall survival rate comprised 56.7±4.2%, 2-year – 39.2±4.3%, 3-year – 30.0±4.1%, 4and 5-year – 26.8±4.0%, 10-year – 15.0±4.4%. The risk of death in patients with primary glioblastoma of the brain was the greatest in the first two years of follow-up from the time of diagnosis. No associations were found with patients’ age and gender, or the side of the tumor lesion. To study the relationship between long-term treatment results and serum GFAP concentrations patients were divided into two groups: 1) patients in whom GFAP was not detected (GFAP-negative) and 2) those with detectable GFAP concentrations (GFAP-positive). Median survival time of 46 GFAP-negative glioblastoma patients was 24.8 months, while in 130 GFAP-positive patients it comprised only 13.7 months (p = 0.047). No differences in the overall survival in GFAP-positive glioblastoma group depending on the serum GFAP concentration were found. The differences in the overall survival depending on the presence or absence of GFAP in blood serum were mostly pronounced in the female group and in patients below 50 years of age. Thus, median survival of GFAP-negative glioblastoma patients below 50 years was several fold higher than in GFAP-positive patients of this age group (70.8 and 12.4 months respectively).
Conclusion. The overall survival of patients with grade IV primary glioblastoma is significantly higher in GFAP-negative than in GFAP-positive group. Hence, the presence of GFAP in blood serum can be regarded as an unfavorable prognostic factor for this disease.
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About the authors
O. N. Kleimenova
Federal State Budgetary Educational Institution of Higher Education «Russian University of Medicine» of the Ministry of Health of Russia
Email: olga_kleimnova@mail.ru
ORCID iD: 0009-0008-0869-8067
SPIN-code: 2470-6642
Post-graduate Student, Department of Clinical Biochemistry and Laboratory Diagnostics
Russian Federation, Dolgorukovskaya street, 4, Moscow, 127006A. A. Alferov
Federal State Budgetary Educational Institution of Higher Education «Russian University of Medicine» of the Ministry of Health of Russia; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
Email: aleksandr.alferov@yahoo.com
ORCID iD: 0000-0003-3585-5693
SPIN-code: 9252-7995
Ph.D. (Med.). Assistant, Department of Clinical Biochemistry and Laboratory Diagnostics
Russian Federation, Dolgorukovskaya street, 4, Moscow, 127006; Kashirskoe highway, 24, Moscow, 115522N. V. Lyubimova
Federal State Budgetary Educational Institution of Higher Education «Russian University of Medicine» of the Ministry of Health of Russia; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
Email: ovkovaleva@gmail.com
ORCID iD: 0000-0003-0430-2754
SPIN-code: 2047-6708
Dr.Sc. (Biol.), Professor, Department of Clinical Biochemistry and Laboratory Diagnostics, Scientific Consultant, Clinical Diagnostic Laboratory
Russian Federation, Dolgorukovskaya street, 4, Moscow, 127006; Kashirskoe highway, 24, Moscow, 115522A. А. Mitrofanov
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
Email: mitrofanov-aa@list.ru
ORCID iD: 0000-0002-4125-7342
SPIN-code: 7155-1982
Ph.D. (Med.), Researcher, Department of Neuro-Oncology
Russian Federation, Kashirskoe highway, 24, Moscow, 115522A. Kh. Bekyashev
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
Email: abekyashev@gmail.com
ORCID iD: 0000-0002-4160-9598
SPIN-code: 1140-1406
Dr.Sc. (Med.), Head Department of Neuro-Oncology
Russian Federation, Kashirskoe highway, 24, Moscow, 115522O. V. Kovaleva
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
Author for correspondence.
Email: ovkovaleva@gmail.com
ORCID iD: 0000-0001-6132-9924
SPIN-code: 9912-4482
Dr.Sc. (Biol.), Senior Researcher, Laboratory of Regulation of Viral and Cellular Oncogenes, Research Institute of Carcinogenesis
Russian Federation, Kashirskoe highway, 24, Moscow, 115522Е. S. Gershtein
Federal State Budgetary Educational Institution of Higher Education «Russian University of Medicine» of the Ministry of Health of Russia; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
Email: esgershtein@gmail.com
ORCID iD: 0000-0002-3321-801X
SPIN-code: 5317-1433
Dr.Sc. (Biol.), Professor, Department of Clinical Biochemistry and Laboratory Diagnostics, Scientific Consultant, Clinical Diagnostic Laboratory
Russian Federation, Dolgorukovskaya street, 4, Moscow, 127006; Kashirskoe highway, 24, Moscow, 115522N. E. Kushlinskii
Federal State Budgetary Educational Institution of Higher Education «Russian University of Medicine» of the Ministry of Health of Russia; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
Email: kne3108@gmail.com
ORCID iD: 0000-0002-3898-4127
SPIN-code: 6225-1487
Dr.Sc. (Med.), Professor, Academician of the Russian Academy of Sciences, Head of the Department of Clinical Biochemistry and Laboratory Diagnostics, Scientific Director of the Clinical Diagnostic Laboratory
Russian Federation, Dolgorukovskaya street, 4, Moscow, 127006; Kashirskoe highway, 24, Moscow, 115522I. S. Stilidi
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia
Email: ronc@list.ru
ORCID iD: 0000-0002-0493-1166
SPIN-code: 9622-7106
Dr.Sc. (Med.), Professor, Academician of the Russian Academy of Sciences, Director
Russian Federation, Kashirskoe highway, 24, Moscow, 115522References
- Barthel P.C., Staabs F., Li L.Y. et al. Immunoreactivity to astrocytes in different forms of dementia: High prevalence of autoantibodies to GFAP. Brain Behav. Immun. Health. 2023; 29: 100609. doi: 10.1016/j.bbih.2023.100609.
- Jung C.S., Foerch C., Schänzer A. et al. Serum GFAP is a diagnostic marker for glioblastoma multiforme. Brain. 2007; 130(Pt 12): 3336–3341. doi: 10.1093/brain/awm263.
- Lyubimova N.V., Toms M.G., Popova E.E. et al. Neurospesific proteins in the serum of patients with brain tumors. Bull. Exp. Biol. Med. 2011; 150(6): 732–734. doi: 10.1007/s10517-011-1236-9.
- Skalli O., Wilhelmsson U., Örndahl C. et al. Astrocytoma grade IV (glioblastoma multiforme) displays 3 subtypes with unique expression profiles of intermediate filament proteins. Human Pathol. 2013; 44(10): 2081–2088. doi: 10.1016/j.humpath.2013.03.013.
- Wang K.K., Yang Z., Yue J.K. et al. Plasma Anti-Glial Fifibrillary Acidic Protein Autoantibody Levels During the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study. J. Neurotrauma. 2016; 33: 1270–1277. doi: 10.1089/neu.2015.3881.
- Bazarian J.J., Welch R.D., Caudle K. et al. Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl-terminal hydrolase L1 test for the prediction of intracranial injuries on head. Acad. Emerg. Med. 2021; 28(11): 1308–1317. doi: 10.1111/acem.14366.
- Wunderlich M.T., Wallesch C.W., Goertler M. Release of glial fibrillary acidic protein is related to the neurovascular status in acute ischemic stroke. Eur. J. Neurol. 2006; 13(10): 1118–1123. doi: 10.1111/j.1468-1331.2006.01435.x.
- Fang H., Hu W., Jiang Z. et al. Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy in Children: A Retrospective Analysis of 35 Cases. Front Immunol. 2021; 12: 761354. doi: 10.3389/fimmu.2021.761354.
- van Asperen J.V., Fedorushkova D.M., Robe P.A.J.T., Hol E.M. Investigation of glial fibrillary acidic protein (GFAP) in body fluids as a potential biomarker for glioma: a systematic review and meta-analysis. Biomarkers. 2022; 27(1): 1–12. doi: 10.1080/1354750X.2021.2006313.
- Anderson N.E., Alexander H.S., Messing A. Alexander disease: the story behind an eponym. J. Hist. Neurosci. 2023; 32(4): 399–422. doi: 10.1080/0964704X.2023.2190354.
- Shen X.N., Huang S.Y., Cui M. et al. Plasma glial fibrillary acidic protein in the alzheimer disease continuum: relationship to other biomarkers, differential diagnosis, and prediction of clinical progression. Clin. Chem. 2023; 69(4): 411–421. doi: 10.1093/clinchem/hvad018.
- Messing A., Brenner M. GFAP at 50. ASN Neuro. 2020. 12:1759091420949680. doi: 10.1177/1759091420949680.
- Zheng X., Yang J., Hou Y. et al. Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP). Eur. J. Med. Res. 2024; 29(1): 51. doi: 10.1186/s40001-023-01631-4.
- Vaz-Salgado M.A., Villamayor M., Albarrán V. et al. Re-current Glioblastoma: A Review of the Treatment Options. Cancers (Basel). 2023; 15(17): 4279. doi: 10.3390/cancers15174279.
- Brown N.F., Ottaviani D., Tazare J. et al. Survival Outcomes and Prognostic Factors in Glioblastoma. Cancers (Basel). 2022; 14(13): 3161. doi: 10.3390/cancers14133161.
- Goyal R., Mathur S.K., Gupta S. et al. Immunohistochemical expression of glial fibrillary acidic protein and CAM5.2 in glial tumors and their role in differentiating glial tumors from metastatic tumors of central nervous system. J. Neurosci. Rural. Pract. 2015; 6(4): 499–503. doi: 10.4103/0976-3147.
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