title: Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia.
abstract: OBJECTIVE
  Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms.
  
  
  METHODS
  A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR.
  
  
  RESULTS
  Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92, and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a, and miR-125b were significantly higher in patients with early colorectal neoplasm than in healthy controls. Elevated levels of miR-21, miR-29a, and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating patients with early colorectal neoplasm from healthy controls were 0.706, 0.741, 0.806, and 0.827, respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who had only small colorectal neoplasms (≤5 mm) than in healthy subjects.
  
  
  CONCLUSIONS
  Because serum levels of miR-21, miR-29a, and miR-125b discriminated patients with early colorectal neoplasm from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia.
authors.affiliation: Center for Gastrointestinal Research, Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horimatsu
authors.affiliation: Center for Gastrointestinal Research, Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas. Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University, Faculty of Medicine, Osaka, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Gastroenterology, Otsu Red Cross Hospital, Shiga, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Honjo
authors.affiliation: Internal Medicine, Kyoto Police Hospital, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ida
authors.affiliation: Digestive Disease Center, The Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Kou
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Kyoto, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kusaka
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Makato
authors.initials: M
authors.lastname: Yagi
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Higurashi
authors.affiliation: Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Yukawa
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Amanuma
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kikuchi
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Muto
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Center for Gastrointestinal Research, Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas. ajay.goel@baylorhealth.edu rickbo@baylorhealth.edu.
authors.forename: C Richard
authors.initials: CR
authors.lastname: Boland
authors.affiliation: Center for Gastrointestinal Research, Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas. ajay.goel@baylorhealth.edu rickbo@baylorhealth.edu.
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D055088:Early Detection of Cancer; D004724:Endoscopy; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C531888:MIRN125 microRNA, human; C524940:MIRN21 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs