title: 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 identification of biomarkers and classification of neurological diseases.
authors.affiliation: Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston Massachusetts 02115, USA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Locasale
authors.forename: Tamar
authors.initials: T
authors.lastname: Melman
authors.forename: Susan
authors.initials: S
authors.lastname: Song
authors.forename: Xuemei
authors.initials: X
authors.lastname: Yang
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Swanson
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Cantley
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wong
authors.forename: John M
authors.initials: JM
authors.lastname: Asara
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000134:cerebrospinal fluid*; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid* / Q000473:pathology; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D005909:Glioblastoma / Q000134:cerebrospinal fluid* / Q000473:pathology; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D009010:Monte Carlo Method; D025341:Principal Component Analysis; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor