Plasma amino acids indicate glioblastoma with ATRX loss

Bobeff, Ernest J.; Szczęsna, Dorota; Bieńkowski, Michał; Janczar, Karolina; Chmielewska-Kassassir, Małgorzata; Wiśniewski, Karol; Papierz, W; Woźniak, Lucyna A.; Jaskólski, Dariusz J.

doi:10.1007/s00726-020-02931-3

Cited by 12 publications

(9 citation statements)

References 62 publications

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“…Molecular movement across the blood-brain barrier is mediated via diffusion, active transport, and carrier-mediated transport, which is particularly used by amino acids. Recently, we demonstrated differences in the levels of certain amino acids in the blood of patients with glioblastoma compared to healthy subjects [25]. The current study, comparing SAH patients with healthy controls, showed that the plasma levels of alanine, glutamic acid, glycine, leucine, methionine, proline, hydroxyproline, tyrosine, and valine differed significantly.…”

Section: Discussionsupporting

confidence: 42%

Plasma Amino Acids May Improve Prediction Accuracy of Cerebral Vasospasm after Aneurysmal Subarachnoid Haemorrhage

Bobeff

Bukowiecka‐Matusiak

Stawiski

et al. 2022

JCM

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Aneurysmal subarachnoid haemorrhages (aSAH) account for 5% of strokes and continues to place a great burden on patients and their families. Cerebral vasospasm (CVS) is one of the main causes of death after aSAH, and is usually diagnosed between day 3 and 14 after bleeding. Its pathogenesis remains poorly understood. To verify whether plasma concentration of amino acids have prognostic value in predicting CVS, we analysed data from 35 patients after aSAH (median age 55 years, IQR 39–62; 20 females, 57.1%), and 37 healthy volunteers (median age 50 years, IQR 38–56; 19 females, 51.4%). Fasting peripheral blood samples were collected on postoperative day one and seven. High performance liquid chromatography-mass spectrometry (HPLC-MS) analysis was performed. The results showed that plasma from patients after aSAH featured a distinctive amino acids concentration which was presented in both principal component analysis and direct comparison. No significant differences were noted between postoperative day one and seven. A total of 18 patients from the study group (51.4%) developed CVS. Hydroxyproline (AUC = 0.7042, 95%CI 0.5259–0.8826, p = 0.0248) and phenylalanine (AUC = 0.6944, 95%CI 0.5119–0.877, p = 0.0368) presented significant CVS prediction potential. Combining the Hunt-Hess Scale and plasma levels of hydroxyproline and phenylalanine provided the model with the best predictive performance and the lowest leave-one-out cross-validation of performance error. Our results suggest that plasma amino acids may improve sensitivity and specificity of Hunt-Hess scale in predicting CVS.

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Section: Discussionsupporting

confidence: 42%

Plasma Amino Acids May Improve Prediction Accuracy of Cerebral Vasospasm after Aneurysmal Subarachnoid Haemorrhage

Bobeff

Bukowiecka‐Matusiak

Stawiski

et al. 2022

JCM

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“…Amino acid metabolism was found disrupted following a nuclear magnetic resonance (NMR)-based metabolomic analysis in plasma samples of glioma patients and healthy controls [ 68 ]. The decreased plasma levels of various amino acids in glioma patients may indicate an increased demand for amino acids at the tumor niche [ 68 , 69 , 70 ]. Synergistically to amino acid metabolism and, in particular, arginine/proline metabolism, the dysregulation of nitrogen and/or pyrimidine metabolism pathways may reflect urea cycle dysregulation, providing essential substrates for tumor proliferation and growth [ 71 , 72 ].…”

Section: Discussionmentioning

confidence: 99%

Bioenergetic Profiling in Glioblastoma Multiforme Patients with Different Clinical Outcomes

et al. 2023

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The accumulation of cell biomass is associated with dramatically increased bioenergetic and biosynthetic demand. Metabolic reprogramming, once thought as an epiphenomenon, currently relates to disease progression, also in response to extracellular fate-decisive signals. Glioblastoma multiforme patients often suffer misdiagnosis, short survival time, low quality of life, and poor disease management options. Today, tumor genetic testing and histological analysis guide diagnosis and treatment. We and others appreciate that metabolites complement translational biomarkers and molecular signatures in disease profiling and phenotyping. Herein, we coupled a mixed-methods content analysis to a mass spectrometry-based untargeted metabolomic analysis on plasma samples from glioblastoma multiforme patients to delineate the role of metabolic remodeling in biological plasticity and, hence, disease severity. Following data processing and analysis, we established a bioenergetic profile coordinated by the mitochondrial function and redox state, lipids, and energy substrates. Our findings show that epigenetic modulators are key players in glioblastoma multiforme cell metabolism, in particular when microRNAs are considered. We propose that biological plasticity in glioblastoma multiforme is a mechanism of adaptation and resistance to treatment which is eloquently revealed by bioenergetics.

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“…The discovery of the Isocitrate Dehydrogenase (IDH) metabolic pathway has revived this antimetabolic approach, which aims at reducing the synthesis of these molecules, which play an essential role in tumor development and progression [61]. Recently differences in the levels of certain amino acids in the blood of patients with glioblastoma compared to healthy subjects have been demonstrated [62]. These data empower the central role of amino acids in the genesis of glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

Integrative Metabolomics Reveals Deep Tissue and Systemic Metabolic Remodeling in Glioblastoma

Gilard

Ferey

Marguet

et al. 2021

Cancers

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(1) Background: Glioblastoma is the most common malignant brain tumor in adults. Its etiology remains unknown in most cases. Glioblastoma pathogenesis consists of a progressive infiltration of the white matter by tumoral cells leading to progressive neurological deficit, epilepsy, and/or intracranial hypertension. The mean survival is between 15 to 17 months. Given this aggressive prognosis, there is an urgent need for a better understanding of the underlying mechanisms of glioblastoma to unveil new diagnostic strategies and therapeutic targets through a deeper understanding of its biology. (2) Methods: To systematically address this issue, we performed targeted and untargeted metabolomics-based investigations on both tissue and plasma samples from patients with glioblastoma. (3) Results: This study revealed 176 differentially expressed lipids and metabolites, 148 in plasma and 28 in tissue samples. Main biochemical classes include phospholipids, acylcarnitines, sphingomyelins, and triacylglycerols. Functional analyses revealed deep metabolic remodeling in glioblastoma lipids and energy substrates, which unveils the major role of lipids in tumor progression by modulating its own environment. (4) Conclusions: Overall, our study demonstrates in situ and systemic metabolic rewiring in glioblastoma that could shed light on its underlying biological plasticity and progression to inform diagnosis and/or therapeutic strategies.

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Plasma amino acids indicate glioblastoma with ATRX loss

Cited by 12 publications

References 62 publications

Plasma Amino Acids May Improve Prediction Accuracy of Cerebral Vasospasm after Aneurysmal Subarachnoid Haemorrhage

Plasma Amino Acids May Improve Prediction Accuracy of Cerebral Vasospasm after Aneurysmal Subarachnoid Haemorrhage

Bioenergetic Profiling in Glioblastoma Multiforme Patients with Different Clinical Outcomes

Integrative Metabolomics Reveals Deep Tissue and Systemic Metabolic Remodeling in Glioblastoma

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