Document Detail


Metabolomics of human cerebrospinal fluid identifies signatures of malignant glioma.
MedLine Citation:
PMID:  22240505     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jason W Locasale; Tamar Melman; Susan Song; Xuemei Yang; Kenneth D Swanson; Lewis C Cantley; Eric T Wong; John M Asara
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-12
Journal Detail:
Title:  Molecular & cellular proteomics : MCP     Volume:  11     ISSN:  1535-9484     ISO Abbreviation:  Mol. Cell Proteomics     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-13     Completed Date:  2012-10-11     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101125647     Medline TA:  Mol Cell Proteomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  M111.014688     Citation Subset:  IM    
Affiliation:
Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Brain Neoplasms / cerebrospinal fluid*,  pathology
Case-Control Studies
Cluster Analysis
Female
Glioblastoma / cerebrospinal fluid*,  pathology
Humans
Male
Metabolome*
Metabolomics
Middle Aged
Monte Carlo Method
Principal Component Analysis
Sensitivity and Specificity
Tandem Mass Spectrometry
Tumor Burden
Tumor Markers, Biological / cerebrospinal fluid*
Grant Support
ID/Acronym/Agency:
3P30CA006516-45S7/CA/NCI NIH HHS; NIH P01 CA120964/CA/NCI NIH HHS; NIH R01-GM41890/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Tumor Markers, Biological
Comments/Corrections

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