Investigations in the possibility of early detection of colorectal cancer by gas chromatography/triple-quadrupole mass spectrometry.
In developed countries, the number of patients with colorectal cancer has been increasing, and colorectal cancer is one of the most common causes of cancer death. To improve the quality of life of colorectal cancer patients, it is necessary to establish novel screening methods that would allow early detection of colorectal cancer. We performed metabolome analysis of a plasma sample set from 282 stage 0/I/II colorectal cancer patients and 291 healthy volunteers using gas chromatography/triple-quadrupole mass spectrometry in an attempt to identify metabolite biomarkers of stage 0/I/II colorectal cancer. The colorectal cancer patients included patients with stage 0 (N=79), I (N=80), and II (N=123) in whom invasion and metastasis were absent. Our analytical system detected 64 metabolites in the plasma samples, and the levels of 29 metabolites differed significantly (Bonferroni-corrected p=0.000781) between the patients and healthy volunteers. Based on these results, a multiple logistic regression analysis of various metabolite biomarkers was carried out, and a stage 0/I/II colorectal cancer prediction model was established. The area under the curve, sensitivity, and specificity values of this model for detecting stage 0/I/II colorectal cancer were 0.996, 99.3%, and 93.8%, respectively. The model's sensitivity and specificity values for each disease stage were >90%, and surprisingly, its sensitivity for stage 0, specificity for stage 0, and sensitivity for stage II disease were all 100%. Our predictive model can aid early detection of colorectal cancer and has potential as a novel screening test for cases of colorectal cancer that do not involve lymph node or distant metastasis.
Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Shin
S
Nishiumi
Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Takashi
T
Kobayashi
Analytical and Measuring Instruments Division, Shimadzu Corporation, Nakagyo-ku, Kyoto 604-8511, Japan.
Shuichi
S
Kawana
Analytical and Measuring Instruments Division, Shimadzu Corporation, Nakagyo-ku, Kyoto 604-8511, Japan.
Yumi
Y
Unno
Analytical and Measuring Instruments Division, Shimadzu Corporation, Nakagyo-ku, Kyoto 604-8511, Japan.
Takero
T
Sakai
Division of Cancer Differentiation, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Koji
K
Okamoto
Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
Yasuhide
Y
Yamada
Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
Kazuki
K
Sudo
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan.
Taiki
T
Yamaji
Endoscopy Division, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
Yutaka
Y
Saito
Department of Colorectal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
Yukihide
Y
Kanemitsu
Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
Natsuko Tsuda
NT
Okita
Division of Screening Assessment and Management, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan.
Hiroshi
H
Saito
Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan.
Shoichiro
S
Tsugane
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Takeshi
T
Azuma
Analytical and Measuring Instruments Division, Shimadzu Corporation, Nakagyo-ku, Kyoto 604-8511, Japan.
Noriyuki
N
Ojima
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan.|Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan.|AMED-CREST, AMED, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Masaru
M
Yoshida
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D016015:Logistic Models; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D012372:ROC Curve; D015203:Reproducibility of Results
D014408:Biomarkers, Tumor
biomarker; colorectal cancer; gas chromatography/triple-quadrupole mass spectrometry; metabolite; metabolomics