title: Epigenetic alteration of DNA in mucosal wash fluid predicts invasiveness of colorectal tumors.
abstract: Although conventional colonoscopy is considered the gold standard for detecting colorectal tumors, accurate staging is often difficult because advanced histology may be present in small colorectal lesions. We collected DNA present in mucosal wash fluid from patients undergoing colonoscopy and then assessed the methylation levels of four genes frequently methylated in colorectal cancers to detect invasive tumors. We found that methylation levels in wash fluid were significantly higher in patients with invasive than those with noninvasive tumors. Cytologic and K-ras mutation analyses suggested that mucosal wash fluid from invasive tumors contained greater numbers of tumor cells than wash fluid from noninvasive tumors. Among the four genes, levels of mir-34b/c methylation had the greatest correlation with the invasion and showed the largest area under the receiver operating characteristic curve (AUC = 0.796). Using cutoff points of mir-34b/c methylation determined by efficiency considerations, the sensitivity/specificity were 0.861/0.657 for the 13.0% (high sensitivity) and 0.765/0.833 for the 17.8% (well-balanced) cutoffs. In the validation test set, the AUC was also very high (0.915), the sensitivity/specificity were 0.870/0.875 for 13.0% and 0.565/0.958 for 17.8%. Using the diagnostic tree constructed by an objective algorithm, the diagnostic accuracy of the invasiveness of colorectal cancer was 91.3% for the training set and 85.1% for the test set. Our results suggest that analysis of the methylation of DNA in mucosal wash fluid may be a good molecular marker for predicting the invasiveness of colorectal tumors.
authors.affiliation: Department of Biochemistry, Sapporo Medical University, Sapporo, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Kamimae
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Hiro-o
authors.initials: HO
authors.lastname: Yamano
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Masami
authors.initials: M
authors.lastname: Ashida
authors.forename: Tomo
authors.initials: T
authors.lastname: Hatahira
authors.forename: Akiko
authors.initials: A
authors.lastname: Sato
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kimura
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Taku
authors.initials: T
authors.lastname: Harada
authors.forename: Seiko
authors.initials: S
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamaru
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kai
authors.forename: Morie
authors.initials: M
authors.lastname: Nishiwaki
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyota
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D057890:Epigenomics; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D009092:Mucous Membrane / Q000166:cytology*; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D035683:MicroRNAs