title: Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer.
abstract: Aberrant DNA methylation could potentially serve as a biomarker for colorectal neoplasms. In this study, we assessed the feasibility of using DNA methylation detected in bowel lavage fluid (BLF) for colorectal cancer screening. A total of 508 BLF specimens were collected from patients with colorectal cancer (n = 56), advanced adenoma (n = 53), minor polyp (n = 209), and healthy individuals (n = 190) undergoing colonoscopy. Methylation of 15 genes (miR-1-1, miR-9-1, miR-9-3, miR-34b/c, miR-124-1, miR-124-2, miR-124-3, miR-137, SFRP1, SFRP2, APC, DKK2, WIF1, LOC386758, and ZNF582) was then analyzed in MethyLight assays, after which receiver operating characteristic (ROC) curves were analyzed to assess the diagnostic performance of BLF methylation. Through analyzing BLF specimens in a training set (n = 345), we selected the three genes showing the greatest sensitivity for colorectal cancer detection (miR-124-3, 71.8%; LOC386758, 79.5%; and SFRP1, 74.4%). A scoring system based on the methylation of those three genes (M-score) achieved 82% sensitivity and 79% specificity, and the area under the ROC curve (AUC) was 0.834. The strong performance of this system was then validated in an independent test set (n = 153; AUC = 0.808). No significant correlation was found between M-score and the clinicopathologic features of the colorectal cancers. Our results demonstrate that DNA methylation in BLF specimens may be a useful biomarker for the detection of colorectal cancer.
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan. Division of Gastroenterology and Hematology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan. Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Hiro-o
authors.initials: HO
authors.lastname: Yamano
authors.affiliation: The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan. Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kumegawa
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Ashida
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Harada
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takagi
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan. Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Aoki
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Nishizono
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Nakaoka
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuyada
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan. Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Niinuma
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kai
authors.affiliation: Division of Gastroenterology and Hematology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimoda
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.affiliation: Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.affiliation: The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.affiliation: Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan. hsuzuki@sapmed.ac.jp.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics; D003111:Colonic Polyps / Q000175:diagnosis* / Q000235:genetics*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D019175:DNA Methylation; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064368:Healthy Volunteers; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009780:Occult Blood; D011127:Polyps; D012372:ROC Curve; D012680:Sensitivity and Specificity; D007507:Therapeutic Irrigation; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor