title: Serum metabolomics analysis for early detection of colorectal cancer.
abstract: BACKGROUND
  Although colorectal cancer (CRC) is one of the most common causes of cancer mortality, early-stage detection improves survival rates dramatically. Because cancer impacts important metabolic pathways, the alteration of metabolite levels as a potential biomarker of early-stage cancer has been the focus of many studies. Here, we used CE-TOFMS, a novel and promising method with small injection volume and high resolution, to separate and detect ionic compounds based on the different migration rates of charged metabolites in order to detect metabolic biomarkers in patients with CRC.
  
  
  METHODS
  A total of 56 patients with CRC (n = 14 each of Stages I-IV), 60 healthy controls, and 59 patients with colonic adenoma were included in this study. Metabolome analysis was conducted by CE-TOFMS on serum samples of patients and controls using the Advanced Scan package (Human Metabolome Technologies).
  
  
  RESULTS
  We obtained 334 metabolites in the serum, of which 139 were identified as known substances. Among these 139 known metabolites, 16 were correlated with CRC stage by upregulation and 44 by downregulation, with benzoic acid (r = -0.649, t = 11.653, p = 6.07599E-24), octanoic acid (r = 0.557, t = 9.183, p = 7.9557E-17), decanoic acid (r = 0.539, t = 8.749, p = 1.24352E-15), and histidine (r = -0.513, t = 8.194, p = 3.90224E-14) exhibiting significant correlation.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first report to determine the correlation between serum metabolites and CRC stage using CE-TOFMS. Our results show that benzoic acid exhibited excellent diagnostic power and could potentially serve as a novel disease biomarker for CRC diagnosis.
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.|Department of Gastroenterology, Murakami Memorial Hospital, Asahi University, 3-23 Hashimotocho Gifu-city, Gifu, 500-8523, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yagi
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Higashimura
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hirai
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okayama
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katada
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kamada
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kuriu
authors.affiliation: Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nakanishi
authors.affiliation: Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan. ynaito@koto.kpu-m.ac.jp.|Department of Endoscopy and Ultrasound Medicine, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan. ynaito@koto.kpu-m.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D009367:Neoplasm Staging
keywords: Benzoic acid; CE-TOFMS; Colorectal cancer; Metabolomics analysis