title: Identification of microRNA-135b in stool as a potential noninvasive biomarker for colorectal cancer and adenoma.
abstract: OBJECTIVE
  Detecting microRNA (miRNA) in stool is a novel approach for colorectal cancer (CRC) screening. This study aimed to identify stool-based miRNA as noninvasive biomarkers for detection of CRC and adenoma.
  
  
  METHODS
  A miRNA expression array covering 667 human miRNAs was performed on five pairs of CRC and two pairs of advanced adenoma tissues. The most upregulated miRNAs were validated in 40 pairs of CRC tissues, 16 pairs of advanced adenoma tissues, and 424 stool samples, including 104 CRCs, 169 adenomas, 42 inflammatory bowel diseases (IBD), and 109 healthy controls. miRNA levels were followed-up after removal of lesions.
  
  
  RESULTS
  In an array analysis, miR-31 and miR-135b were the most upregulated miRNAs in CRC and advanced adenoma as compared with their adjacent normal tissues (>13-fold increase). In stool samples, level of miR-135b was significantly higher in subjects with CRC (P < 0.0001) or adenomas (P < 0.0001), but not in patients with IBD compared with controls. miR-135b showed a significant increasing trend across the adenoma to cancer sequence (P < 0.0001). Levels of miR-31 were not significantly different among groups. The sensitivity of stool mR-135b was 78% for CRC, 73% for advanced adenoma, and 65% for any adenoma, respectively, with a specificity of 68%. No significant difference in the miR-135b level was found between proximal and distal colorectal lesions. Stool miR-135b dropped significantly upon removal of CRC or advanced adenoma (P < 0.0001).
  
  
  CONCLUSIONS
  Stool-based miR-135b can be used as a noninvasive biomarker for the detection of CRC and advanced adenoma. Clin Cancer Res; 20(11); 2994-3002. ©2014 AACR.
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, ChinaAuthors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Chung Wah
authors.initials: CW
authors.lastname: Wu
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Siew Chien
authors.initials: SC
authors.lastname: Ng
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, ChinaAuthors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Linwei
authors.initials: L
authors.lastname: Tian
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Simon Siu Man
authors.initials: SS
authors.lastname: Ng
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Wing Wa
authors.initials: WW
authors.lastname: Leung
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Wai Tak
authors.initials: WT
authors.lastname: Law
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, ChinaAuthors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Tung On
authors.initials: TO
authors.lastname: Yau
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Francis Ka Leung
authors.initials: FK
authors.lastname: Chan
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China.
authors.forename: Joseph Jao Yiu
authors.initials: JJ
authors.lastname: Sung
authors.affiliation: Authors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, ChinaAuthors' Affiliations: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences; Department of Surgery; Stanley Ho Center for Emerging Infectious Disease, the Chinese University of Hong Kong, Hong Kong; and Gastrointestinal Cancer Biology and Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China junyu@cuhk.edu.hk.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C544965:MIRN135 microRNA, human; D035683:MicroRNAs