Single Nucleotide Polymorphism (rs4932178) in the P1 Promoter of FURIN Is Not Prognostic to Colon Cancer

Biomed Res Int. 2015:2015:321276. doi: 10.1155/2015/321276. Epub 2015 Jun 7.

Abstract

High expression of the proprotein processing enzyme FURIN has been associated with tumor progression and metastasis. A SNP (rs4932178) in the promoter of FURIN has been reported to affect expression in liver, with the T allele resulting in higher expression than the C allele. In this study we have investigated the association of this SNP with prognostic and biological subgroups of colorectal cancer (CRC). In a panel of 1382 patients with CRC, this SNP had no impact on overall survival or on postoperative risk of relapse. This SNP also could not be linked with FURIN expression levels in CRC samples from the patients. Furthermore, we demonstrate in luciferase reporter experiments in the colon cancer cell lines Caco-2 and SW480 and in the hepatocellular carcinoma cell line Huh 7 that expression is not affected by the SNP. Since, FURIN inhibition in human colon cancer cell lines has previously been shown to repress tumor metastases, association between FURIN gene expression levels and postoperative relapse-free survival was also investigated. However, no association could be found. Altogether, we could not confirm an effect of the SNP on FURIN expression in vitro and no correlations could be found in vivo with FURIN expression or outcome.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Line, Tumor
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Furin / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Polymorphism, Single Nucleotide
  • Prognosis*
  • Promoter Regions, Genetic

Substances

  • Furin