Deep sequencing of circulating exosomal microRNA allows non-invasive glioblastoma diagnosis

Ebrahimkhani, Saeideh; Vafaee, Fatemeh; Hallal, Susannah; Wei, Heng; Lee, Maggie Yuk T.; Young, Paul E.; Satgunaseelan, Laveniya; Shivalingam, Brindha; Suter, Catherine M.; Buckland, Michael E.; Kaufman, Kimberley L.

doi:10.1101/342154

Cited by 26 publications

(48 citation statements)

References 35 publications

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“…They also observed that the serum exosomal miR-301a levels were lower after surgical resection of the tumour, but were increased during GBM recurrence, indicating that serum exosomal miR-301a could be a potential biomarker for diagnosis/prognosis for GBM patients. 127,128 Ebrahimkhani et al 129 used a panel of seven exosomal miRNAs-miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p and miR-543-to differentiate GBM patients from healthy controls with an accuracy rate of 91.7%. In addition, Santangelo et al 91 analysed a miRNA signature in exosomes from the serum of glioma patients in an attempt to differentiate tumour grading and gliomas from brain metastases.…”

Section: Microvesicles In Glioblastomamentioning

confidence: 99%

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: 99%

Circulating biomarkers in patients with glioblastoma

et al. 2019

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“…The microRNAs selected for this project have all previously been studied in glioblastoma, either in total serum or EVs [ 19 , 20 , 34 , 35 , 36 ]. While some of these papers report that the majority of extracellular microRNAs are found bound to Ago [ 14 ], other studies claim that the majority of extracellular microRNAs are found inside small or large EVs [ 15 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Serum miRNA in Glioblastoma Patients: CD44-Based Enrichment of Extracellular Vesicles Enhances Specificity for the Prognostic Signature

Tzaridis

Reiners

Weller

et al. 2020

IJMS

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Glioblastoma is a devastating disease, for which biomarkers allowing a prediction of prognosis are urgently needed. microRNAs have been described as potentially valuable biomarkers in cancer. Here, we studied a panel of microRNAs in extracellular vesicles (EVs) from the serum of glioblastoma patients and evaluated their correlation with the prognosis of these patients. The levels of 15 microRNAs in EVs that were separated by size-exclusion chromatography were studied by quantitative real-time PCR, followed by CD44 immunoprecipitation (SEC + CD44), and compared with those from the total serum of glioblastoma patients (n = 55) and healthy volunteers (n = 10). Compared to total serum, we found evidence for the enrichment of miR-21-3p and miR-106a-5p and, conversely, lower levels of miR-15b-3p, in SEC + CD44 EVs. miR-15b-3p and miR-21-3p were upregulated in glioblastoma patients compared to healthy subjects. A significant correlation with survival of the patients was found for levels of miR-15b-3p in total serum and miR-15b-3p, miR-21-3p, miR-106a-5p, and miR-328-3p in SEC + CD44 EVs. Combining miR-15b-3p in serum or miR-106a-5p in SEC + CD44 EVs with any one of the other three microRNAs in SEC + CD44 EVs allowed for a prognostic stratification of glioblastoma patients. We have thus identified four microRNAs in glioblastoma patients whose levels, in combination, can predict the prognosis for these patients.

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“…were generated using Next Generation Sequencing technology, enabling reliable quantification of in particular low‐abundance miRNAs. Circulating miRNAs were found to be stable even under conditions as harsh as boiling, extreme pH, long‐time storage at room temperature, and multiple freeze‐thaw cycles . Details regarding sample collection, sample preparation, sequencing, and data processing can be found in Krauskopf et al ., and see for patient characteristics and levels of liver damage markers.…”

Section: Methodsmentioning

confidence: 99%

Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease

Bohler

Liu

Krauskopf

et al. 2019

Clinical Translational Sci

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Four complementary approaches were used to investigate acetaminophen overdose as a risk factor for Parkinson's disease (PD). Circulating microRNAs (miRNAs) serum profiles from acetaminophen-overdosed patients were compared with patients with terminal PD, revealing four shared miRNAs. Similarities were found among molecular structures of dopamine (DA), acetaminophen, and two known PD inducers indicating affinity for dopaminergic transport. Potential interactions between acetaminophen and the human DA transporter were confirmed by molecular docking modeling and binding free energy calculations. Thus, it is plausible that acetaminophen is taken up by the dopaminergic transport system into the substantia nigra (SN). A ChEMBL query identified proteins that are similarly targeted by DA and acetaminophen. Here, we highlight CYP3A4, present in the SN, a predominant metabolizer of acetaminophen into its toxic metabolite N-acetyl-p-benzoquinone imine and shown to be regulated in PD. Overall, based on our results, we hypothesize that overdosing of acetaminophen is a potential risk factor for parkinsonism.Parkinson's disease (PD) affects about 0.5% of the population aged 60-69, 1% aged 70-79, and up to 2% aged above 80 years of age. 1 Familial mutations are responsible for ~ 10% of PD cases, leaving 90% sporadic cases for which causes are poorly understood. The toxicant 1-methyl-4-phenylpyridinium (MPP + ) is taken up by dopamine (DA) transporters (DATs) 2 and known to induce parkinsonism, which implies that exogenous factors may indeed induce PD. In addition, environmental toxicants, including pesticides (e.g., Paraquat), pollutants (metals and organochlorides), as well as dietary contaminants and drugs, such as methamphetamine (METH) have been suggested to cause sporadic PD. 3,4 Acetaminophen is a widely used analgesic/antipyretic agent. Although acetaminophen is relatively safe when used at therapeutic doses, acetaminophen poisonings are quite frequent. In fact, acetaminophen is responsible for >70,000 visits to the hospital and is responsible for around 300-400 deaths/year in the United States alone. 5 Acetaminophen toxicity is also a major issue in acetaminophen-opioid products, which led the US Food and Drug Administration (FDA) to limit the dose of acetaminophen in these combinations to 325 mg/ dose. 5 Hepatocellular injury due to formation of reactive metabolites is considered as a hallmark of acetaminophen toxicity. In rodent studies, acetaminophen has been shown to also cause damage to the brain, although it is not entirely clear

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Deep sequencing of circulating exosomal microRNA allows non-invasive glioblastoma diagnosis

Cited by 26 publications

References 35 publications

Circulating biomarkers in patients with glioblastoma

Circulating biomarkers in patients with glioblastoma

Analysis of Serum miRNA in Glioblastoma Patients: CD44-Based Enrichment of Extracellular Vesicles Enhances Specificity for the Prognostic Signature

Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease

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