title: The prognostic significance of APC gene mutation and miR-21 expression in advanced-stage colorectal cancer.
abstract: OBJECTIVE
  Colorectal cancer (CRC) is the second commonest cause of cancer death in Taiwan. Although numerous genes have been associated with tumorigenesis in colorectal cancer, only a few have been validated and used as biomarkers for predicting clinical outcome. The aim of this study was to analyse the association of APC gene mutation and miR-21 expression with clinical outcome in CRC patients.
  
  
  METHODS
  In total, 195 colorectal cancer patients were enrolled in a single medical centre between 2003 and 2007. APC gene mutation and expression of APC and miR-21 were analysed by direct DNA sequencing and real-time reverse transcription polymerase chain reaction. The primary outcome included 5-year overall survival and univariate (Kaplan-Meier) and multivariate (Cox regression) analyses of prognostic factors.
  
  
  RESULTS
  The results showed that 66 (33.8%) of 195 tumour tissues contained an APC mutation. The predominant APC gene variations were deletion mutations (50.0%). APC gene expression was low in CRC and negatively correlated with miR-21 expression and gene mutation. In advanced-stage cancer, patients with APC mutation/high miR-21 had poorer overall survival rates than those with APC mutation/low miR-21, APC wild-type/high miR-21 and APC wild-type/low miR-21.
  
  
  CONCLUSIONS
  In Taiwan, downregulation of the APC gene in CRC correlated with gene mutation and miR-21 upregulation. APC mutation and miR-21 expression could be used to predict the clinical outcome of CRC, especially in patients with advanced disease.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: T-H
authors.initials: TH
authors.lastname: Chen
authors.forename: S-W
authors.initials: SW
authors.lastname: Chang
authors.forename: C-C
authors.initials: CC
authors.lastname: Huang
authors.forename: K-L
authors.initials: KL
authors.lastname: Wang
authors.forename: K-T
authors.initials: KT
authors.lastname: Yeh
authors.forename: C-N
authors.initials: CN
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: C-C
authors.initials: CC
authors.lastname: Lin
authors.forename: Y-W
authors.initials: YW
authors.lastname: Cheng
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000368:Aged; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D009154:Mutation; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D015996:Survival Rate; D060449:Wnt Signaling Pathway
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: APC; miR-21; prognostic factor