Cerebrospinal fluid VEGF levels and angiogenic capacity as potential prognostic markers in patients with gliomas: a pilot study

Vera, Sergio; Sinning, Mariana; Vergara, Marcela; Lemus, David; Rosas, Carlos

doi:10.1007/s11060-019-03314-9

Cited by 5 publications

(12 citation statements)

References 35 publications

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“…3) Patients with a GBM diagnosis that showing high expression of VEGF (>30) and CD133 (>1.2), in 80% of the cases a PFS of <4 months was observed. Our results agree with several papers considering lower levels of these biomarkers on longer PFS 25 26 28 and higher levels on shorter PFS. 25 26 28 33 – 35…”

Section: Discussionsupporting

confidence: 93%

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Utility of gene tumor expression ofVEGF, FOXM1*3andCD-133on diagnosis and prognosis of brain gliomas

Feria-Romero

Nettel-Rueda

Rodríguez-Florido

et al. 2020

Preprint

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Objective. This paper seeks to quantify the normalized expression of transcripts FOXM1*3, VEGF, CD133, and MGMT and their relation with the histopathological and molecular diagnosis and with the probability of estimating tumor progression-free survival of gliomas. Methods. A cohort of patients was made up of patients aged over 18 years with a histological and molecular diagnosis of gliomas from the year 2011 to 2018. The patients had a complete tumor resection. Patients with high-grade glioma received adjuvant management (temozolamide and radiotherapy). Clinical and imaging follow-up was carried out periodically to identify the time of progression free survival (PFS). Results. Ninety-one patients (age range, 18-85 years) comprised the study cohort with a predominance of males. The expression of FOXM1*3, VEGF, and CD133 allowed the differentiation of astrocytomas grade II from GBM. ROC curves proved statistically significant in the GBM model (p <0.05), demonstrating greatest sensitivity with FOXM1*3 (91%), and greatest specificity with VEGF (93%). The age-adjusted Cox multivariate model established that a PFS50% of 25 months corresponds to a median value of 5.3 for VEGF and 0.42 for CD133. Conclusions The normalized expression of transcripts FOXM1*3, VEGF, and CD133 allow us to estimate the probability of PFS, especially in gliomas grades II and IV; likewise, their overexpression defines the diagnosis of GBM.

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Section: Discussionsupporting

confidence: 93%

“…In contrast to the reports previously cited, in this work the expression of mRNA VEGF normalized with IPO8 permitted differentiating between low-grade (A II) and high-grade astrocytomas (A III and GBM) which agrees with Yang et al, (2016)25 and other authors with different techniques of VEGF evaluation. 26 – 28…”

Section: Discussionmentioning

confidence: 99%

Utility of gene tumor expression ofVEGF, FOXM1*3andCD-133on diagnosis and prognosis of brain gliomas

Feria-Romero

Nettel-Rueda

Rodríguez-Florido

et al. 2020

Preprint

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“…63 Our study identified increased concentrations of VEGF in CSF of dogs with neoplastic or inflammatory disease relative to samples from dogs with non-neoplastic, noninflammatory disorders and particularly high concentrations in a subset of dogs with gliomas, choroid plexus tumors, and primitive neuroectodermal tumors. Increased VEGF concentrations in the CSF have been documented in humans with gliomas 61,64,65 and leptomeningeal metastasis of primary tumors originating outside of the CNS. [66][67][68] Cerebrospinal fluid VEGF concentrations were higher in high-grade gliomas than in low-grade gliomas 61,65 or other CNS neoplasms.…”

Section: Discussionmentioning

confidence: 99%

“…Increased VEGF concentrations in the CSF have been documented in humans with gliomas 61,64,65 and leptomeningeal metastasis of primary tumors originating outside of the CNS. [66][67][68] Cerebrospinal fluid VEGF concentrations were higher in high-grade gliomas than in low-grade gliomas 61,65 or other CNS neoplasms. 64 The reason for the variability in CSF VEGF concentrations in dogs with neoplastic CNS disease is unknown.…”

Section: Discussionmentioning

confidence: 99%

“… 9 , 11 Tissue concentrations also have been shown to vary by tumor subtype and grade in meningiomas 56 , 57 and gliomas 54 , 55 , 58 of humans and this has been reflected in differences in CSF concentrations in some studies. 61 , 64 , 65 It is likely that tissue VEGF concentrations varied based on the grade of these tumors and may have been reflected in the CSF concentrations. Consistent and reliable tumor grading was not available in the pathology reports for all dogs included in our study and therefore was not addressed.…”

Section: Discussionmentioning

confidence: 99%

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Vascular endothelial growth factor concentrations in the cerebrospinal fluid of dogs with neoplastic or inflammatory central nervous system disorders

Mariani

Niman

Boozer

et al. 2021

Veterinary Internal Medicne

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Background: Vascular endothelial growth factor (VEGF) is a key molecular driver of angiogenesis and vascular permeability and is expressed by a wide variety of neoplasms. Although blood VEGF concentrations have been quantified in intracranial tumors of dogs, cerebrospinal fluid (CSF) VEGF concentration might be a more sensitive biomarker of disease.Objective: Concentrations of VEGF in CSF are higher in dogs with central nervous system (CNS) neoplasia compared to those with meningoencephalomyelitis and other neurologic disorders.Animals: One hundred and twenty-six client-owned dogs presented to a veterinary teaching hospital.Methods: Case-control study. Cerebrospinal fluid was archived from dogs diagnosed with CNS neoplasia and meningoencephalomyelitis. Control dogs had other neurological disorders or diseases outside of the CNS. A commercially available kit was used to determine VEGF concentrations.Results: Detectable CSF VEGF concentrations were present in 49/63 (77.8%) neoplastic samples, 22/24 (91.7%) inflammatory samples, and 8/39 (20.5%) control samples. The VEGF concentrations were significantly different between groups (P < .0001), and multiple comparison testing showed that both neoplastic and inflammatory groups had significantly higher concentrations than did controls (P < .05), but did not differ from each other. Gliomas and choroid plexus tumors had significantly higher VEGF concentrations than did the control group (P < .05).Conclusions and Clinical Importance: Cerebrospinal fluid VEGF concentrations may serve as a marker of neoplastic and inflammatory CNS disorders relative to other conditions.

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Cerebrospinal fluid cytokine levels are associated with macrophage infiltration into tumor tissues of glioma patients

et al. 2021

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Background Diffuse gliomas are the most common malignant tumors of the central nervous system with poor treatment efficacy. Infiltration of immune cells into tumors during immunosurveillance is observed in multiple tumor entities and often associated with a favorable outcome. The aim of this study was to evaluate the infiltration of immune cells in gliomas and their association with cerebrospinal fluid (CSF) cytokine concentrations. Methods We applied immunohistochemistry in tumor tissue sections of 18 high-grade glioma (HGG) patients (4 anaplastic astrocytoma, IDH-wildtype WHO-III; 14 glioblastomas (GBM), IDH-wildtype WHO-IV) in order to assess and quantify leucocytes (CD45) and macrophages (CD68, CD163) within the tumor core, infiltration zone and perivascular spaces. In addition, we quantified the concentrations of 30 cytokines in the same patients’ CSF and in 14 non-inflammatory controls. Results We observed a significantly higher percentage of CD68+ macrophages (21–27%) in all examined tumor areas when compared to CD45+ leucocytes (ca. 3–7%); CD163+ cell infiltration was between 5 and 15%. Compared to the tumor core, significantly more macrophages and leucocytes were detectable within the perivascular area. The brain parenchyma showing a lower tumor cell density seems to be less infiltrated by macrophages. Interleukin (IL)-7 was significantly downregulated in CSF of GBM patients compared to controls. Additionally, CD68+ macrophage infiltrates showed significant correlations with the expression of eotaxin, interferon-γ, IL-1β, IL-2, IL-10, IL-13, IL-16 and vascular endothelial growth factor. Conclusions Our findings suggest that the infiltration of lymphocytes is generally low in HGG, and does not correlate with cytokine concentrations in the CSF. In contrast, macrophage infiltrates in HGG are associated with CSF cytokine changes that possibly shape the tumor microenvironment. Although results point towards an escape from immunosurveillance or even exploitation of immune cells by HGG, further studies are necessary to decipher the exact role of the immune system in these tumors.

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Cerebrospinal fluid VEGF levels and angiogenic capacity as potential prognostic markers in patients with gliomas: a pilot study

Cited by 5 publications

References 35 publications

Utility of gene tumor expression ofVEGF, FOXM1*3andCD-133on diagnosis and prognosis of brain gliomas

Utility of gene tumor expression ofVEGF, FOXM1*3andCD-133on diagnosis and prognosis of brain gliomas

Vascular endothelial growth factor concentrations in the cerebrospinal fluid of dogs with neoplastic or inflammatory central nervous system disorders

Cerebrospinal fluid cytokine levels are associated with macrophage infiltration into tumor tissues of glioma patients

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