title: High expression of miR-181c as a predictive marker of recurrence in stage II colorectal cancer.
abstract: BACKGROUND
  A standard treatment for stage II colorectal cancer (CRC) is surgical resection without adjuvant chemotherapy. However, the recurrence rate of these patients is approximately 20%. To date, there are no robust biomarkers suitable for predicting recurrence in stage II CRC patients. In this study, microRNAs (miRNAs) extracted from CRC tissues were examined for a possible biomarker to predict recurrence in stage II CRC patients.
  
  
  RESULTS
  From the comprehensive analysis, 15 miRNAs were selected as candidates for further study. Regarding let-7a, -7d, -7e, miR-23c, -26b, -128a, -151-5p, and -181c, recurrence rates in training cohort patients with higher expression of these miRNAs isolated from their frozen tissues samples were significantly higher than those with lower expression (P < 0.05). According to multivariate analysis, the higher expression of miR-181c was detected as an independent predictive factor of recurrence (P = 0.001, OR: 9.43, 95% CI: 2.57-34.48). Results were similar in miR-181c extracted from FFPE tissues obtained from the training cohort (P = 0.003, OR: 7.46, 95% CI: 1.97-28.57). In the validation cohort using FFPE tissues, the recurrence rate in patients with higher miR-181c expression was significantly higher than those with lower miR-181c expression (P < 0.001).
  
  
  METHODS
  Comprehensive analysis using a highly sensitive miRNA chip was initially performed to select candidate miRNAs associated with recurrence. Candidate miRNAs were analyzed by real-time RT-PCR using RNA from frozen and formalin-fixed, paraffin-embedded (FFPE) tissues.
  
  
  CONCLUSIONS
  Higher expression of miR-181c may be a useful recurrence predictor of stage II CRC patients.
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.|Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Yamazaki
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Koga
authors.affiliation: Pathology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Pathology Division, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Colorectal Surgery Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Kanemitsu
authors.affiliation: Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Saito
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C540193:MIrn181 microRNA, human; D035683:MicroRNAs
keywords: colorectal cancer; miR-181c; predictor of recurrence; tissue microRNA