A novel serum metabolomics-based diagnostic approach for colorectal cancer.
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.


RESULTS
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%).


CONCLUSIONS
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.
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Shin
S
Nishiumi
Takashi
T
Kobayashi
Atsuki
A
Ikeda
Tomoo
T
Yoshie
Megumi
M
Kibi
Yoshihiro
Y
Izumi
Tatsuya
T
Okuno
Nobuhide
N
Hayashi
Seiji
S
Kawano
Tadaomi
T
Takenawa
Takeshi
T
Azuma
Masaru
M
Yoshida
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001224:Aspartic Acid / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D003538:Cystamine / Q000097:blood; D055088:Early Detection of Cancer; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000592:standards; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007737:Kynurenine / Q000097:blood; D016015:Logistic Models; D008293:Malates / Q000097:blood; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D015999:Multivariate Analysis; D012372:ROC Curve; D012015:Reference Standards; D018709:Statistics, Nonparametric
C502920:2-isopropylmalic acid; D014408:Biomarkers, Tumor; D006885:Hydroxybutyrates; D008293:Malates; D001224:Aspartic Acid; D007737:Kynurenine; C031570:2-hydroxybutyric acid; D003538:Cystamine