Glial Fibrillary Acidic Protein in the Diagnosis and Prognosis of Malignant Glial Tumors

Lyubimova, N. V.; Timofeev, Yu. S.; Митрофанов, А. А.; Bekyashev, А. Kh.; Гончарова, З. А.; Кушлинский, Н. Е.

doi:10.1007/s10517-020-04741-9

Cited by 10 publications

(36 citation statements)

References 11 publications

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“…The diagnostic and prognostic value of serum GFAP has been investigated in patients with glioma 23‐25 and other neurological conditions, 16,17 but only few studies have focused on BM 14,26 . GFAP serum levels seem to be higher in patients with high‐grade glioma than with BM 24,25 .…”

Section: Discussionmentioning

confidence: 99%

Serum glial fibrillary acidic protein is a predictor of brain metastases in patients with metastatic breast cancer

Darlix

Hirtz

Mollévi

et al. 2021

Intl Journal of Cancer

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In patients with metastatic breast cancer (MBC), brain metastases (BM) are associated with high morbidity and mortality. However, there is no validated serum biomarker that accurately predicts BM occurrence in these patients, and the role of serum biomarkers for prognosis remains unclear. Here, we evaluated the association of neurofilament light chain (NfL), ubiquitin C‐terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP) and tau serum levels with BM presence and prognosis in patients with MBC. In serum samples from patients with MBC with (n = 100) and without BM (n = 47), we measured the biomarker serum levels using single molecule array (Simoa) technology (Neurology‐4‐Plex assay). To evaluate their accuracy to identify patients with BM, we determined the receiver operating characteristic curve and the area under the curve (AUC) for each biomarker and calculated their sensitivity and specificity. The median serum levels of NfL, UCHL1, tau and GFAP were significantly higher in patients with BM. The AUC for GFAP (0.82, 95% confidence interval [CI] 0.75‐0.88) was significantly higher than those of the other biomarkers considered independently. Using the medians as cutoff values, elevated serum levels of NfL, UCHL1, tau and GFAP were associated with BM in univariate analysis, but only high GFAP levels in multivariate analysis (odd ratio 23.4, 95% CI 6.8‐80.5, P < .001). Elevated serum GFAP levels were independently associated with poor outcome. GFAP outperforms NfL, UCHL1 and tau as diagnostic and prognostic factor of BM in patients with MBC. These results must now be validated in an independent cohort of patients.

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Section: Discussionmentioning

confidence: 99%

Serum glial fibrillary acidic protein is a predictor of brain metastases in patients with metastatic breast cancer

Darlix

Hirtz

Mollévi

et al. 2021

Intl Journal of Cancer

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“…Similar to other structural neurological diseases, a large body of evidence indicates that blood GFAP levels are elevated in individuals with brain tumours. Some studies have found blood GFAP levels to be higher in participants with glioblastoma multiforme (GBM) than in healthy control participants, participants with other non-glial primary tumours and participants with brain metastasis [111][112][113][114][115] , whereas, in other studies, a statistically significant difference in blood GFAP levels between participants with high-grade (that is, GBM) and low-grade brain tumours was not detected 116,117 . In participants with GBM, blood GFAP concentration correlated with preoperative tumour volume 111,112,114,118,119 , volume of necrosis 111,119 and GFAP expression levels in tumour tissue 111,119 .…”

Section: Brain Tumoursmentioning

confidence: 96%

Blood GFAP as an emerging biomarker in brain and spinal cord disorders

et al. 2022

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In 2018, the FDA authorized the use of a blood test for glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in mild traumatic brain injury (mTBI), crowning a long success story of CNS-driven blood biomarker development [1][2][3] . Initial efforts to identify fluid biomarkers for neurological diseases focused on the cerebrospinal fluid (CSF) as, compared with blood, CSF is closer to the brain extracellular space and contains higher concentrations of CNS-derived proteins 4 . The establishment of fourth-generation immune assays in the last decade 3,5 brought the possibility of quickly obtaining rapid and robust protein biomarker measurements from blood samples, opening up new perspectives in the field of CNS-derived markers. For example, levels of classic CSF biomarkers of neuroaxonal damage, such as neurofilament light chain (NfL) 5 , phosphorylated tau 217 (ref. 6), and UCH-L1 (ref. 7 ) can now be readily quantified in blood, indicating that these markers hold potential for use in diagnosis and monitoring of disease activity, and as surrogate end points for treatment trials. The literature on the utility of blood GFAP as a biomarker is also growing, reinforcing the large body of published data on CSF GFAP 3,[8][9][10][11][12][13][14] . The evaluation of blood levels of GFAP has the potential to enable the in vivo longitudinal evaluation of different aspects of the astrocytic response in several neurological disorders. Here, we provide an up-to-date review of the analytical aspects, current evidence, perspectives, and limitations of blood GFAP as a biomarker, with the purpose of outlining how to refine its application in the diagnosis and monitoring of neurological diseases. GFAP biology and analysisAstrocytes represent around 30-40% of the cells in the CNS 15 , form an integral part of the blood-brain barrier (BBB) and establish numerous interactions with other cells in the nervous system, including neurons.

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“…GFAP diagnostic specificities were more uniform and ranged between 85-100% (80,82,84). However, GFAP concentrations were not elevated in the circulation of glioma patients with tumor grades lower than grade IV (80,82,85).…”

Section: Gfapmentioning

confidence: 91%

“…Furthermore, GFAP was increased in patients with glioblastoma as compared to patients with lower tumor grades (38,80,(82)(83)(84)(85)87) and in glioblastoma patients compared to patients with other brain pathologies such as brain metastases, meningioma or pituitary adenoma (38,81,82,(84)(85)(86)88). Also, GFAP levels were increased in patients with worse survival (80,84), greater tumor volume (40,80,82,86,88), higher Ki67 proliferation index and lack of IDH1-mutation (80). However, it was not always confirmed that circulating GFAP is correlated to tumor volume and survival (83).…”

Section: Gfapmentioning

confidence: 98%

“…As both usually do not occur in non-acute brain diseases such as multiple sclerosis or brain metastases, GFAP may be a specific marker for gliomas. Indeed, GFAP values (38,80,(82)(83)(84)(85) were found to be elevated in glioblastoma patients, but diagnostic sensitivities were rather variable: between 33% and 86% of glioblastoma had elevated GFAP concentrations (38,(82)(83)(84)(85)(86).…”

Section: Gfapmentioning

confidence: 99%

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Blood-Based Biomarkers for Glioma in the Context of Gliomagenesis: A Systematic Review

et al. 2021

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BackgroundGliomas are the most common and aggressive tumors of the central nervous system. A robust and widely used blood-based biomarker for glioma has not yet been identified. In recent years, a plethora of new research on blood-based biomarkers for glial tumors has been published. In this review, we question which molecules, including proteins, nucleic acids, circulating cells, and metabolomics, are most promising blood-based biomarkers for glioma diagnosis, prognosis, monitoring and other purposes, and align them to the seminal processes of cancer.MethodsThe Pubmed and Embase databases were systematically searched. Biomarkers were categorized in the identified biomolecules and biosources. Biomarker characteristics were assessed using the area under the curve (AUC), accuracy, sensitivity and/or specificity values and the degree of statistical significance among the assessed clinical groups was reported.Results7,919 references were identified: 3,596 in PubMed and 4,323 in Embase. Following screening of titles, abstracts and availability of full-text, 262 articles were included in the final systematic review. Panels of multiple biomarkers together consistently reached AUCs >0.8 and accuracies >80% for various purposes but especially for diagnostics. The accuracy of single biomarkers, consisting of only one measurement, was far more variable, but single microRNAs and proteins are generally more promising as compared to other biomarker types.ConclusionPanels of microRNAs and proteins are most promising biomarkers, while single biomarkers such as GFAP, IL-10 and individual miRNAs also hold promise. It is possible that panels are more accurate once these are involved in different, complementary cancer-related molecular pathways, because not all pathways may be dysregulated in cancer patients. As biomarkers seem to be increasingly dysregulated in patients with short survival, higher tumor grades and more pathological tumor types, it can be hypothesized that more pathways are dysregulated as the degree of malignancy of the glial tumor increases. Despite, none of the biomarkers found in the literature search seem to be currently ready for clinical implementation, and most of the studies report only preliminary application of the identified biomarkers. Hence, large-scale validation of currently identified and potential novel biomarkers to show clinical utility is warranted.

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Glial Fibrillary Acidic Protein in the Diagnosis and Prognosis of Malignant Glial Tumors

Cited by 10 publications

References 11 publications

Serum glial fibrillary acidic protein is a predictor of brain metastases in patients with metastatic breast cancer

Serum glial fibrillary acidic protein is a predictor of brain metastases in patients with metastatic breast cancer

Blood GFAP as an emerging biomarker in brain and spinal cord disorders

Blood-Based Biomarkers for Glioma in the Context of Gliomagenesis: A Systematic Review

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