Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer.


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.

DOI: 10.1158/1940-6207.CAPR-14-0162

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@article{Harada2014AnalysisOD, title={Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer.}, author={Taku Harada and Eiichiro Yamamoto and Hiro-o Yamano and Masanori Nojima and Reo Maruyama and Kohei Kumegawa and Masami Ashida and Kenjiro Yoshikawa and Tomoaki Kimura and Eiji Harada and Ryo Takagi and Yoshihito Tanaka and Hironori Aoki and Masayo Nishizono and Michiko Nakaoka and Akihiro Tsuyada and Takeshi Niinuma and Masahiro Kai and Kazuya Shimoda and Yasuhisa Shinomura and Tamotsu Sugai and Kohzoh Imai and Hiromu Suzuki}, journal={Cancer prevention research}, year={2014}, volume={7 10}, pages={1002-10} }