MoCadb-logoMoCadb - Study ID Exp26342311

PubMed ID26342311
AuthorsZhu J(1), Djukovic D(1), Deng L(1)(2), Gu H(1), Himmati F(1), Abu Zaid M(3), Chiorean EG(3)(4), Raftery D(5)(6).
TitleTargeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring.
JournalAnal Bioanal Chem. 2015 Oct;407(26):7857-63.
AbstractColorectal cancer (CRC) is one of the most prevalent cancers worldwide and a major cause of human morbidity and mortality. In addition to early detection, close monitoring of disease progression in CRC can be critical for patient prognosis and treatment decisions. Efforts have been made to develop new methods for improved early detection and patient monitoring; however, research focused on CRC surveillance for treatment response and disease recurrence using metabolomics has yet to be reported. In this proof of concept study, we applied a targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolic profiling approach focused on sequential metabolite ratio analysis of serial serum samples to monitor disease progression from 20 CRC patients. The use of serial samples reduces patient to patient metabolic variability. A partial least squares-discriminant analysis (PLS-DA) model using a panel of five metabolites (succinate, N2, N2-dimethylguanosine, adenine, citraconic acid, and 1-methylguanosine) was established, and excellent model performance (sensitivity = 0.83, specificity = 0.94, area under the receiver operator characteristic curve (AUROC) = 0.91 was obtained, which is superior to the traditional CRC monitoring marker carcinoembryonic antigen (sensitivity = 0.75, specificity = 0.76, AUROC = 0.80). Monte Carlo cross validation was applied, and the robustness of our model was clearly observed by the separation of true classification models from the random permutation models. Our results suggest the potential utility of metabolic profiling for CRC disease monitoring.

Sample characteristics

SpeciesTissue / SourceCompartmentDiseaseNDetection methodSample
Homo sapiensbloodserumCRC progression (DP)20LC-MS/MSDem26342311a, Dem26342311b

Sample description and preparation

N (case)10
N (control)10
Disease (case)CRC progression (DP)
Disease (control)CR+SD

Sample analysis

Software thresholdP<0.05

Molecule list

Molecule IDextExternal IDNameSource accRegulation (case/control)Scores
CHEBI15729 15729L-OrnithineOrnithineratio: 0.91p-value: 0.025
CHEBI15741 15741succinic acidSuccinateratio: 1.33p-value: 0.0028
CHEBI16169 16169homogentisateHomogentisateratio: 1.19p-value: 0.028
CHEBI16708 16708adenineAdenineratio: 1.11p-value: 0.0049
CHEBI17626 17626citraconic acidCitraconic Acidratio: 1.58p-value: 0.0049
CHEBI17755 17755CystathionineCystathionineratio: 0.65p-value: 0.016
CHEBI17775 17775urateUrateratio: 1.15p-value: 0.018
CHEBI18148 18148alpha-D-glucose 1,6-bisphosphateG16BPratio: 1.05p-value: 0.032
CHEBI19062 190621-Methylguanosine1-Methylguanosineratio: 1.25p-value: 0.0084
CHEBI19289 19289N2,N2-DimethylguanosineN2,N2-Dimethylguanosineratio: 1.34p-value: 0.0037
CHEBI22211 22211aconitic acidAconitateratio: 1.45p-value: 0.014
CHEBI28061 28061D-GalactoseGalactoseratio: 0.36p-value: 0.032
CHEBI28602 28602beta-D-fructofuranose 2,6-bisphosphateF16BP/F26BPratio: 1.03p-value: 0.049
CHEBI30744 30744Oxalacetic acidOxaloacetateratio: 1.3p-value: 0.043
CHEBI30860 30860methylmalonic acidMethylmalonateratio: 1.31p-value: 0.0049
CHEBI32816 32816Pyruvic acidPyruvateratio: 0.64p-value: 0.043
CHEBI37024 370242-aminoadipic acid2-Aminoadipateratio: 1.38p-value: 0.049
CHEBI86269 862693-nitrotyrosine3-Nitro-tyrosineratio: 0.84p-value: 0.012
CHEBI89843 89843Methylsuccinic acidMethylsuccinateratio: 0.8p-value: 0.032

Compile date 10-20-2017© .