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A novel serum metabolomics-based diagnostic approach for colorectal cancer.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (7), pp. e40459. Date of Electronic Publication: 2012 Jul 11. - Publication Year :
- 2012
-
Abstract
- Background: To improve the quality of life of colorectal cancer patients, it is important to establish new screening methods for early diagnosis of colorectal cancer.<br />Methodology/principal Findings: We performed serum metabolome analysis using gas-chromatography/mass-spectrometry (GC/MS). First, the accuracy of our GC/MS-based serum metabolomic analytical method was evaluated by calculating the RSD% values of serum levels of various metabolites. Second, the intra-day (morning, daytime, and night) and inter-day (among 3 days) variances of serum metabolite levels were examined. Then, serum metabolite levels were compared between colorectal cancer patients (N = 60; N = 12 for each stage from 0 to 4) and age- and sex-matched healthy volunteers (N = 60) as a training set. The metabolites whose levels displayed significant changes were subjected to multiple logistic regression analysis using the stepwise variable selection method, and a colorectal cancer prediction model was established. The prediction model was composed of 2-hydroxybutyrate, aspartic acid, kynurenine, and cystamine, and its AUC, sensitivity, specificity, and accuracy were 0.9097, 85.0%, 85.0%, and 85.0%, respectively, according to the training set data. In contrast, the sensitivity, specificity, and accuracy of CEA were 35.0%, 96.7%, and 65.8%, respectively, and those of CA19-9 were 16.7%, 100%, and 58.3%, respectively. The validity of the prediction model was confirmed using colorectal cancer patients (N = 59) and healthy volunteers (N = 63) as a validation set. At the validation set, the sensitivity, specificity, and accuracy of the prediction model were 83.1%, 81.0%, and 82.0%, respectively, and these values were almost the same as those obtained with the training set. In addition, the model displayed high sensitivity for detecting stage 0-2 colorectal cancer (82.8%).<br />Conclusions/significance: Our prediction model established via GC/MS-based serum metabolomic analysis is valuable for early detection of colorectal cancer and has the potential to become a novel screening test for colorectal cancer.
- Subjects :
- Adult
Aged
Aged, 80 and over
Area Under Curve
Aspartic Acid blood
Case-Control Studies
Cystamine blood
Early Detection of Cancer
Female
Gas Chromatography-Mass Spectrometry standards
Humans
Hydroxybutyrates blood
Kynurenine blood
Logistic Models
Malates blood
Male
Metabolomics
Middle Aged
Multivariate Analysis
ROC Curve
Reference Standards
Statistics, Nonparametric
Biomarkers, Tumor blood
Colorectal Neoplasms blood
Colorectal Neoplasms diagnosis
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22792336
- Full Text :
- https://doi.org/10.1371/journal.pone.0040459