The prognostic significance of APC gene mutation and miR-21 expression in advanced-stage colorectal cancer

Colorectal Dis. 2013 Nov;15(11):1367-74. doi: 10.1111/codi.12318.

Abstract

Aim: 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.

Method: 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.

Conclusion: 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.

Keywords: APC; miR-21; prognostic factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Aged
  • Colorectal Neoplasms / chemistry
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Down-Regulation
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Genes, APC*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / analysis
  • MicroRNAs / genetics*
  • Mutation
  • Neoplasm Staging
  • Proportional Hazards Models
  • RNA, Messenger / analysis
  • Survival Rate
  • Wnt Signaling Pathway

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Messenger