Metabolomic signature of brain cancer

Abstract

Despite advances in surgery and adjuvant therapy, brain tumours represent one of the leading causes of cancer-related mortality and morbidity in both adults and children. Gliomas constitute about 60% of all cerebral tumours, showing varying degrees of malignancy. They are difficult to treat due to dismal prognosis and limited therapeutics. Metabolomics is the untargeted and targeted analyses of endogenous and exogenous small molecules, which characterizes the phenotype of an individual. This emerging “omics” science provides functional readouts of cellular activity that contribute greatly to the understanding of cancer biology including brain tumour biology. Metabolites are highly informative as a direct signature of biochemical activity; therefore, metabolite profiling has become a promising approach for clinical diagnostics and prognostics. The metabolic alterations are well-recognized as one of the key hallmarks in monitoring disease progression, therapy and revealing new molecular targets for effective therapeutic intervention. Taking advantage of the latest high-throughput analytical technologies, i.e. nuclear magnetic resonance spectroscopy and mass spectrometry, metabolomics is now a promising field for precision medicine and drug discovery. In the present report, we review the application of metabolomics and in vivo metabolic profiling in the context of adult gliomas and paediatric brain tumours. Analytical platforms such as high-resolution nuclear magnetic resonance, in vivo magnetic resonance spectroscopic imaging and high- and low-resolution mass spectrometry are discussed. Moreover, the relevance of metabolic studies in the development of new therapeutic strategies for treatment of gliomas are reviewed.

Circulating tumour DNA, microRNA and metabolites in cerebrospinal fluid as biomarkers for central nervous system malignancies

“…Once produced, they can be measured in tissue as well as biological fluids like blood, plasma, CSF, urine and sweat. Abnormal levels of metabolites might suggest the existence of a disease process 70. At the time of this review, the HMDB lists 450 metabolites that have been identified in CSF.…”

Amino acid metabolism‐related gene expression‐based risk signature can better predict overall survival for glioma

“…In our study, we focused on gliomas, the most common form of primary malignant brain tumor, which can be subdivided into grades II‐IV in light of WHO classification. Compared with WHO Grades II‐III, which comprise LGG, GBM WHO IV bears a dismal prognosis with median survival rates of 14.6 months . The 2016 WHO classification of central nervous system (CNS) tumors combines molecular parameters and histology to define diffuse gliomas .…”

CEST‐MRI for glioma pH quantification in mouse model: Validation by immunohistochemistry

“…The study was focused on glioma, an aggressive cerebral tumor characterized by a typical poor prognosis. In glioma acidic pHe is well known to regulate proliferation, angiogenesis, immunosuppression, invasion and chemoresistance, pathophysiological processes that are at the basis of its high heterogeneity. Therefore, a robust imaging method that would allow the quantification of the glioma pHe is of great interest.…”

“…Despite optimal treatment consisting of maximal resection followed by radiation and chemotherapy, virtually all tumors quickly recur . A feature commonly present in GBM, as in many other tumors, is the onset of a highly glycolytic metabolism with the presence of an acid extracellular microenvironment . The chaotic and irregular vasculature occurring in the tumor region leads to an unbalanced blood supply with a consequent transient or chronic hypoxia .…”