title: Stromal expression of miR-21 in T3-4a colorectal cancer is an independent predictor of early tumor relapse.
abstract: BACKGROUND
  MicroRNA-21 (miR-21) is an oncogenic microRNA that regulates the expression of multiple cancer-related target genes. miR-21 has been associated with progression of some types of cancer. Metastasis-associated protein1 expression and loss of E-cadherin expression are correlated with cancer progression and metastasis in many cancer types. In advanced colorectal cancer, the clinical significance of miR-21 expression remains unclear. We aimed to investigate the impact of miR-21 expression in advanced colorectal cancer and its correlation with target proteins associated with colorectal cancer progression.
  
  
  METHODS
  From 2004 to 2007, 277 consecutive patients with T3-4a colorectal cancer treated with R0 surgical resection were included. Patients with neoadjuvant therapy and distant metastasis at presentation were excluded. The expression of miR-21 was investigated by in situ hybridization. Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression.
  
  
  RESULTS
  High stromal expression of miR-21 was found in 76 of 277 (27.4%) colorectal cancer samples and was correlated with low E-cadherin expression (P = 0.019) and high metastasis-associated protein1 expression (P = 0.004). T3-4a colorectal cancer patients with high miR-21 expression had significantly shorter recurrence-free survival than those with low miR-21 expression. When analyzing colon and rectal cancer separately, high expression of miR-21 was an independent prognostic factor of unfavorable recurrence-free survival in T3-4a colon cancer patients (P = 0.038, HR = 2.45; 95% CI = 1.05-5.72) but not in T3-4a rectal cancer patients. In a sub-classification analysis, high miR-21 expression was associated with shorter recurrence-free survival in the stage II cancer (P = 0.001) but not in the stage III subgroup (P = 0.267).
  
  
  CONCLUSIONS
  Stromal miR-21 expression is related to the expression of E-cadherin and metastasis-associated protein1 in colorectal cancer. Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.
authors.affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. wonkkang@catholic.ac.kr.
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Kang
authors.affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Jinkwon.Lee@catholic.ac.kr.
authors.forename: Jin Kwon
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. stoh@catholic.ac.kr.
authors.forename: Seong Taek
authors.initials: ST
authors.lastname: Oh
authors.affiliation: Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 137-701, Republic of Korea. hakjjang@catholic.ac.kr.
authors.forename: Sung Hak
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 137-701, Republic of Korea. ckjung@catholic.ac.kr.
authors.forename: Chan Kwon
authors.initials: CK
authors.lastname: Jung
mesh_terms: D000368:Aged; D015820:Cadherins / Q000032:analysis; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006655:Histone Deacetylases / Q000032:analysis; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry*; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D012097:Repressor Proteins / Q000032:analysis; D012307:Risk Factors; D015534:Trans-Activators
chemical_list: D015820:Cadherins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases