Investigations in the possibility of early detection of colorectal cancer by gas chromatography/triple-quadrupole mass spectrometry

// Shin Nishiumi 1, * , Takashi Kobayashi 1, * , Shuichi Kawana 2 , Yumi Unno 2 , Takero Sakai 2 , Koji Okamoto 3 , Yasuhide Yamada 4 , Kazuki Sudo 4 , Taiki Yamaji 5 , Yutaka Saito 6 , Yukihide Kanemitsu 7 , Natsuko Tsuda Okita 4 , Hiroshi Saito 8 , Shoichiro Tsugane 9 , Takeshi Azuma 1 , Noriyuki Ojima 2 , Masaru Yoshida 1, 10, 11  1 Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan  2 Analytical and Measuring Instruments Division, Shimadzu Corporation, Nakagyo-ku, Kyoto 604-8511, Japan  3 Division of Cancer Differentiation, National Cancer Center Research Institute, Tokyo 104-0045, Japan  4 Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan  5 Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan  6 Endoscopy Division, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan  7 Department of Colorectal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan  8 Division of Screening Assessment and Management, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan  9 Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan 10 Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan 11 AMED-CREST, AMED, Chuo-ku, Kobe, Hyogo 650-0017, Japan * These authors have contributed equally to this work Correspondence to: Masaru Yoshida, email: myoshida@med.kobe-u.ac.jp Keywords: metabolomics, colorectal cancer, biomarker, gas chromatography/triple-quadrupole mass spectrometry, metabolite Received: November 14, 2016      Accepted: January 09, 2017      Published: February 04, 2017 ABSTRACT 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.