title: Circulating microRNA-203 predicts prognosis and metastasis in human colorectal cancer.
abstract: Distant metastasis is a major cause of deaths in patients with colorectal cancer (CRC), which is partly due to lack of robust metastasis-predictive biomarkers. In spite of the important function of microRNA (miR)-203 in cancer metastasis, its clinical significance in CRC metastasis remains unknown. Here, we evaluated the potential role of serum miR-203 as a non-invasive biomarker for CRC metastasis.
  
  
  
  MiR-203 expression was quantified by quantitative reverse-transcription PCR in 58 pairs of primary CRC (pCRC) and corresponding matched liver metastasis (LM), as well as 186 serum and 154 matched tissue specimens from patients with CRC in cohort 1. Next, we performed validation of miR-203 levels in serum from 144 patients with CRC in an independent cohort (cohort 2). Mouse models of CRC-associated metastases were established to identify the source of circulating miR-203. Expression patterns of miR-203 in tissues were determined by in situ hybridisation.
  
  
  
  MiR-203 expression was significantly upregulated in LM compared with matched pCRC tissues. Serum miR-203 levels were significantly upregulated in a stage-dependent manner, and high miR-203 expression was associated with poor survival in patients with CRC in both patient cohorts. Increased miR-203 levels in serum indicated high risk for poor prognosis (HR=2.1), as well as metastasis to lymph nodes (OR=2.5), liver (OR=6.2), peritoneum (OR=7.2) and distant organs (OR=4.4). Serum miR-203 levels were significantly higher in animals with liver or systemic metastasis compared with controls.
  
  
  
  High levels of serum miR-203 associate with poor survival and metastasis, suggesting it to be a promising non-invasive prognostic and metastasis-predictive biomarker in patients with CRC.
authors.affiliation: Center for Gastrointestinal Cancer Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.|Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.|BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Keun
authors.identifier: 0000-0002-6944-2718
authors.initials: K
authors.lastname: Hur
authors.affiliation: Center for Gastrointestinal Cancer Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.|Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.affiliation: Center for Gastrointestinal Cancer Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Ide
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Imaoka
authors.affiliation: Center for Gastrointestinal Cancer Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: C Richard
authors.initials: CR
authors.lastname: Boland
authors.affiliation: Center for Gastrointestinal Cancer Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000097:blood* / Q000235:genetics / Q000556:secondary*; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C546703:MIRN203 microRNA, human; D035683:MicroRNAs
keywords: COLON CARCINOGENESIS; COLORECTAL CANCER