Metabolic alterations in meningioma reflect the clinical course

Abstract

Background Meningiomas are common brain tumours that are usually defined by benign clinical course. However, some meningiomas undergo a malignant transformation and recur within a short time period regardless of their World Health Organization (WHO) grade. The current study aimed to identify potential markers that can discriminate between benign and malignant meningioma courses. Methods We profiled the metabolites from 43 patients with low- and high-grade meningiomas. Tumour specimens were analyzed by nuclear magnetic resonance analysis; 270 metabolites were identified and clustered with the AutoPipe algorithm. Results We observed two distinct clusters marked by alterations in glycine/serine and choline/tryptophan metabolism. Glycine/serine cluster showed significantly lower WHO grades and proliferation rates. Also progression-free survival was significantly longer in the glycine/serine cluster. Conclusion Our findings suggest that alterations in glycine/serine metabolism are associated with lower proliferation and more recurrent tumours. Altered choline/tryptophan metabolism was associated with increases proliferation, and recurrence. Our results suggest that tumour malignancy can be reflected by metabolic alterations, which may support histological classifications to predict the clinical outcome of patients with meningiomas.

Induced senescence and calcification in anaplastic meningioma

“…Higher serotonin content and lower kynurenine in grade 1 compared to grades 2 and 3 were found by mass spectrometry analysis of meningioma metabolites [28]. Clusters with high expression of tryptophan metabolites, including kynurenine acid, indicated predominantly worse prognosis than clusters with low expression [29], based on detailed mass spectrometry results. These studies support our ndings that the proliferative capacity of tumors is altered by a shift in the tryptophan metabolic pathway.…”

Beyond the WHO classification of meningioma: using molecular diagnostics to guide management

“…A metabolomic study by Masalha W et al identified two clusters of meningioma samples marked by metabolite alterations that separated samples by WHO grades, proliferation and PFS [ 29 ]. Another study demonstrated that meningioma metabolome provides a way of identifying aggressive meningioma allowing for personalised treatment [ 30 ].…”

Metabolomic and Lipidomic Characterization of Meningioma Grades Using LC–HRMS and Machine Learning

“…To date, there are minimal data regarding biomarkers that can be used for early diagnostic and prognostic purposes of meningiomas. Proteomics has been used to investigate disease pathophysiology and develop surrogate disease markers for brain tumors; however, only a few studies have examined protein profiling of meningioma tumor specimens. − On the other hand, several metabolomic studies have been conducted on meningioma tissue biopsies using nuclear magnetic resonance (NMR) spectrometry. − In a recent targeted metabolomics study performed by Bender et al using NMR, significantly elevated concentrations of acetate, threonine, ascorbate, scylloinositol, myoinositol, and total choline and low concentrations of glucose, aspartate, isoleucine, valine, adenosine, alanine, and arginine were associated with meningiomas which had poor histologic prognostic markers . The authors also showed that metabolomics analysis could be helpful to differentiate between clinically aggressive meningiomas and those that did not recur after the initial treatment .…”

“…The authors also showed that metabolomics analysis could be helpful to differentiate between clinically aggressive meningiomas and those that did not recur after the initial treatment . In another study conducted by Masalha et al, metabolites of tumor specimens from 43 patients with low- and high-grade meningiomas were analyzed by NMR, and 270 metabolites were identified . Based on that study, alterations in glycine/serine metabolism were associated with lower proliferation (meningioma grade I) and more recurrent grade I tumors, whereas altered choline/tryptophan metabolism was associated with increased proliferation and recurrence .…”

“…In another study conducted by Masalha et al, metabolites of tumor specimens from 43 patients with low- and high-grade meningiomas were analyzed by NMR, and 270 metabolites were identified . Based on that study, alterations in glycine/serine metabolism were associated with lower proliferation (meningioma grade I) and more recurrent grade I tumors, whereas altered choline/tryptophan metabolism was associated with increased proliferation and recurrence . Although these studies provided valuable insights into meningiomas, no previous studies have examined untargeted metabolomics and lipidomics of meningioma tissue biopsies for assessing tumor grades and determining optimum treatment strategies.…”