application of mirna expression analysis on exfoliated colonocytes for diagnosis of colorectal cancer

Satoru Murata1, Yoshikatsu Koga2, Yoshihiro Moriya3, Takayuki Akasu3, Shin Fujita3, Seiichiro Yamamoto3, Yasuo Kakugawa4, Yosuke Ohtake4, Norio Saito1, Yasuhiro Matsumura21Colorectal Surgery Division, Department of Surgical Oncology, National Cancer Center Hospital East, Kashiwa, Japan 2Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan 3Department of Surgery, National Cancer Center Hospital, Tokyo, Japan 4Cancer Screening Division, National Cancer Center Research Center for Cancer Prevention and Screening, Tokyo, JapanBackground: Several methods for the early detection of colorectal cancer to reduce its mortality rate have been reported. Here, we investigated the potential of a fecal micro RNA test for the early detection of colorectal cancer.Methods: Patients with colorectal cancer (n = 299) and healthy volunteers (n = 116) with no abnormalities detected by screening colonoscopy were enrolled in this case-control study. Micro RNA expression in the colonocytes of patients with colorectal cancer (n = 47) and in healthy volunteers (n = 35) were analyzed in the training set, and the micro RNA expression in the colonocytes of patients with colorectal cancer (n = 252) and healthy volunteers (n = 81) was validated in the validation set.Results: In the training study, significant differences in the relative expression level of miR-17-92 cluster, -106a, -135, and -146a were observed between patients with colorectal cancer and healthy volunteers (P < 0.01). The area under the receiver operating characteristic curve using miR-17, -18a, -19a, -19b, -20a, -92a, -106a, -135b, and -146a was more than 0.7. The overall sensitivity and specificity in the training study using these micro RNAs was 70.2% (33/47) and 74.3% (26/35), respectively. The overall sensitivity and specificity in the validation study was 67.5% (170/252) and 75.3% (61/81), respectively.Conclusion: We have developed a fecal micro RNA test for exfoliated colonocytes for colorectal cancer screening. Further comparative study of this test for colorectal cancer screening is needed.Keywords: colorectal cancer, fecal micro RNA, colonocytes, cancer screening, fecal RNA test