Metabolomics of Human Cerebrospinal Fluid Identifies Signatures of Malignant Glioma

Abstract

Cerebrospinal fluid is routinely collected for the diagnosis and monitoring of patients with neurological malignancies. However, little is known as to how its constituents may change in a patient when presented with a malignant glioma. Here, we used a targeted mass-spectrometry based metabolomics platform using selected reaction monitoring with positive/negative switching and profiled the relative levels of over 124 polar metabolites present in patient cerebrospinal fluid. We analyzed the metabolic profiles from 10 patients presenting malignant gliomas and seven control patients that did not present malignancy to test whether a small sample size could provide statistically significant signatures. We carried out multiple unbiased forms of classification using a series of unsupervised techniques and identified metabolic signatures that distinguish malignant glioma patients from the control patients. One subtype identified contained metabolites enriched in citric acid cycle components. Newly diagnosed patients segregated into a different subtype and exhibited low levels of metabolites involved in tryptophan metabolism, which may indicate the absence of an inflammatory signature. Together our results provide the first global assessment of the polar metabolic composition in cerebrospinal fluid that accompanies malignancy, and demonstrate that data obtained from high throughput mass spectrometry technology may have suitable predictive capabilities for the

Cell Metabolomics

“…Consequently, the development of robust metabolomic platforms will greatly facilitate various applications of cell cultures, and would be invaluable tools for gaining insights into these areas. A variety of analytical platforms has been developed to facilitate these and other types of metabolomics experiments (Locasale et al, 2012). For instance, NMR, GC, and LC have been coupled to MS detection methods in order to perform metabolomic profiling of a variety of biological samples (Qin et al, 2012).…”

Analysis of plasma free amino acid profiles in canine brain tumors

“…When comparing human patients and dogs with brain tumors, certain amino acids, including Ala, Pro and Ile, were increased in the two species according to the present and previous studies (13,19,20). By contrast, specific amino acids, such as Met, taurine, Lys, Ser, Phe and Gln were increased only in human patients (13,19).…”

“…By contrast, specific amino acids, such as Met, taurine, Lys, Ser, Phe and Gln were increased only in human patients (13,19). This difference between levels in humans and dogs may be due to the source of the sample.…”

“…These results suggest that the PFAA profile in the peripheral blood reflects brain tumor metabolism. It has been suggested that certain amino acids are associated with human brain tumor metabolism (19). In cerebrospinal fluid (CSF) analysis of human patients with brain tumors, there were significantly higher levels of Pro, Met, taurine, Lys, Ser, Phe and Gln among patients with malignant glioma compared with those in the controls (19).…”

“…It has been suggested that certain amino acids are associated with human brain tumor metabolism (19). In cerebrospinal fluid (CSF) analysis of human patients with brain tumors, there were significantly higher levels of Pro, Met, taurine, Lys, Ser, Phe and Gln among patients with malignant glioma compared with those in the controls (19). In another study, amino acid levels in surgically removed glioma and peritumoral tissues were measured, and significantly increased levels of Ile and Val were identified within the peritumoral tissue compared with those in normal brain tissue (13).…”