Initial evidence that blood-borne microvesicles are biomarkers for recurrence and survival in newly diagnosed glioblastoma patients

Evans, Sydney M.; Putt, Mary; Yang, Xiang-Yang; Lustig, Robert A.; Martinez‐Lage, Maria; Williams, Dewight; Desai, Arati; Brem, Steven; Koch, Cameron J.

doi:10.1007/s11060-015-2051-3

Cited by 40 publications

(31 citation statements)

References 29 publications

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“…In blood collected from seven healthy controls or 11 patients with GBM at different treatment times, the quantity of MVs from patients with stable disease or pseudoprogression was significantly lower than in patients who underwent true tumour progression. 117 Evans et al 118 also correlated an increase in MV number with poor overall survival and with earlier disease recurrence. Skog et al, 119 having isolated MVs from tumour samples and serum of 25 GBM patients by centrifugation, identified the EGFRvIII deletion variant in MVs from seven out of the 25 patients, whereas no EGFRvIII was detected in the control healthy group.…”

Section: Microvesicles In Glioblastomamentioning

confidence: 95%

Circulating biomarkers in patients with glioblastoma

et al. 2019

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Gliomas are the most common tumours of the central nervous system and the most aggressive form is glioblastoma (GBM). Despite advances in treatment, patient survival remains low. GBM diagnosis typically relies on imaging techniques and postoperative pathological diagnosis; however, both procedures have their inherent limitations. Imaging modalities cannot differentiate tumour progression from treatment-related changes that mimic progression, known as pseudoprogression, which might lead to misinterpretation of therapy response and delay clinical interventions. In addition to imaging limitations, tissue biopsies are invasive and most of the time cannot be performed over the course of treatment to evaluate 'real-time' tumour dynamics. In an attempt to address these limitations, liquid biopsies have been proposed in the field. Blood sampling is a minimally invasive procedure for a patient to endure and could provide tumoural information to guide therapy. Tumours shed tumoural content, such as circulating tumour cells, cell-free nucleic acids, proteins and extracellular vesicles, into the circulation, and these biomarkers are reported to cross the blood-brain barrier. The use of liquid biopsies is emerging in the field of GBM. In this review, we aim to summarise the current literature on circulating biomarkers, namely circulating tumour cells, circulating tumour DNA and extracellular vesicles as potential non-invasively sampled biomarkers to manage the treatment of patients with GBM.

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Section: Microvesicles In Glioblastomamentioning

confidence: 95%

Circulating biomarkers in patients with glioblastoma

et al. 2019

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“…In this context, extracellular vesicles could play an important role both for research and clinical purposes. Extracellular vesicles are small structures (50-1,000 nm) surrounded by a lipid membrane bilayer, released in the extracellular space from normal and neoplastic cells (3)(4)(5). Extracellular vesicles include exosomes (50-150 nm, originating from the endosomal pathway) and microvesicles (up to 1,000 nm, shed from the plasma membrane).…”

Section: Introductionmentioning

confidence: 99%

“…Extracellular vesicles include exosomes (50-150 nm, originating from the endosomal pathway) and microvesicles (up to 1,000 nm, shed from the plasma membrane). Their cargo encompasses proteins, RNA, and lipids specific for the cell of origin (3)(4)(5). In the neoplastic setting, they induce tumor progression and infiltration, sustain neoangiogenesis, inhibit immune response, and lead to chemo/radio-resistance (3,(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…Their cargo encompasses proteins, RNA, and lipids specific for the cell of origin (3)(4)(5). In the neoplastic setting, they induce tumor progression and infiltration, sustain neoangiogenesis, inhibit immune response, and lead to chemo/radio-resistance (3,(6)(7)(8)(9)(10)(11)(12). Interestingly, extracellular vesicles can be used as circulating biomarkers because they can be easily isolated from bloodstream, urine, cerebrospinal, ascitic, amniotic, and seminal fluid (4).…”

Section: Introductionmentioning

confidence: 99%

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Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients

Osti

Bene

Rappa

et al. 2019

Clinical Cancer Research

184

126

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Purpose: Glioblastoma (GBM) is the most common primary brain tumor. The identification of blood biomarkers reflecting the tumor status represents a major unmet need for optimal clinical management of patients with GBM. Their high number in body fluids, their stability, and the presence of many tumor-associated proteins and RNAs make extracellular vesicles potentially optimal biomarkers. Here, we investigated the potential role of plasma extracellular vesicles from patients with GBM for diagnosis and follow-up after treatment and as a prognostic tool. Experimental Design: Plasma from healthy controls (n ¼ 33), patients with GBM (n ¼ 43), and patients with different central nervous system malignancies (n ¼ 25) were collected. Extracellular vesicles were isolated by ultracentrifugation and characterized in terms of morphology by transmission electron microscopy, concentration, and size by nanoparticle tracking analysis, and protein composition by mass spectrometry. An orthotopic mouse model of human GBM confirmed human plasma extracellular vesicle quantifications. Associations between plasma extracellular vesicle concentration and clinicopathologic features of patients with GBM were analyzed. All statistical tests were two-sided. Results: GBM releases heterogeneous extracellular vesicles detectable in plasma. Plasma extracellular vesicle concentration was higher in GBM compared with healthy controls (P < 0.001), brain metastases (P < 0.001), and extra-axial brain tumors (P < 0.001). After surgery, a significant drop in plasma extracellular vesicle concentration was measured (P < 0.001). Plasma extracellular vesicle concentration was also increased in GBM-bearing mice (P < 0.001). Proteomic profiling revealed a GBM-distinctive signature. Conclusions: Higher extracellular vesicle plasma levels may assist in GBM clinical diagnosis: their reduction after GBM resection, their rise at recurrence, and their protein cargo might provide indications about tumor, therapy response, and monitoring.

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“…Intriguing evidence showing an increase of EV number associated with poor prognosis, suggest that EV kinetics may be valuable in management of patients with GBM IV (24). Nevertheless, few studies investigated exosome miRNA expression in serum of patients with glioma so far.…”

Section: Exosome Mirnas As Biomarkers For Gliomasmentioning

confidence: 99%

Circulating microRNAs as emerging non-invasive biomarkers for gliomas

Santangelo¹,

Tamanini²,

Cabrini³

et al. 2017

Ann. Transl. Med.

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No single circulating biomarker has been put to practice for malignant gliomas so far, the most lethal primary brain tumors. Many promising protein biomarkers such as the mutant EGFRvIII or glial fibrillary acidic protein (GFAP) have already been detected in the blood and cerebrospinal fluid (CSF) of patients with gliomas, but their clinical value is still pending validation. Furthermore, these and other proteins seem to lack sufficient sensitivity and specificity required for a successful biomarker in this clinical setting. The expression profiling of microRNAs (miRNAs) has already entered cancer clinics as diagnostic and prognostic biomarkers, for assessing tumor initiation, progression and response to treatment. Largescale miRNA expression analyses reported both up-regulation and down-regulation of several miRNAs in tumour tissues from patients with gliomas compared to normal brain tissue, thus supporting the development of miRNA-based biomarkers. Using comprehensive high-throughput approaches, such as microarrays, different circulating miRNAs were proposed as potential biomarkers of gliomas. This review is aimed to summarize the clinical evidence about circulating miRNA biomarkers discovered to date. Mandatory issues to develop clinically validated biomarkers to improve time of diagnosis, predicting response to treatment and prognosis of patients with gliomas are also herein addresses.

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Initial evidence that blood-borne microvesicles are biomarkers for recurrence and survival in newly diagnosed glioblastoma patients

Cited by 40 publications

References 29 publications

Circulating biomarkers in patients with glioblastoma

Circulating biomarkers in patients with glioblastoma

Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients

Circulating microRNAs as emerging non-invasive biomarkers for gliomas

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