title: Single Nucleotide Polymorphism (rs4932178) in the P1 Promoter of FURIN Is Not Prognostic to Colon Cancer.
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.
authors.affiliation: Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Declercq
authors.affiliation: Digestive Oncology Unit, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Jacobs
authors.affiliation: Digestive Oncology Unit, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Biesmans
authors.affiliation: Oncosurgery Unit, University Hospital of Geneva, 1204 Geneva, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Roth
authors.affiliation: Swiss Group for Clinical Cancer Research (SAKK) Coordinating Center, 3008 Bern, Switzerland.
authors.forename: Dirk
authors.initials: D
authors.lastname: Klingbiel
authors.affiliation: Digestive Oncology Unit, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Sabine
authors.initials: S
authors.lastname: Tejpar
authors.affiliation: Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
authors.forename: John W
authors.initials: JW
authors.lastname: Creemers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D045683:Furin / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D045683:Furin