title: A single nucleotide polymorphism in EZH2 predicts overall survival rate in patients with cholangiocarcinoma.
abstract: Cholangiocarcinoma (CCA) is a deadly disease arising from the malignant transformation of cholangiocytes. Enhancer of zeste homolog 2 (EZH2) is overexpressed in poorly differentiated CCA. Functional single nucleotide polymorphisms (SNPs) in this gene may affect the role of EZH2 in cholangiocarcinogenesis and chemoresistance. The aim of the current study was to evaluate the correlation between EZH2 SNPs and clinical outcome. Using PROMO3.0, GeneCard and MicroSNiper, 4 EZH2 SNPs with functional relevance in CCA were selectedin silico. These SNPs were studied in genomic DNA extracted from the blood samples of 75 patients with advanced CCA, who were treated with epirubicin-cisplatin-xeloda (ECX regimen). SNP genotyping was performed with specific PCR assays. The rs887569 TT genotype was correlated with a significantly longer overall survival (OS; TT vs. CT-CC, P=0.026). Moreover, the TT genotype revealed a trend toward a significant association with a reduced risk of mortality (HR, 0.59; 95% CI, 0.33-1.05; P=0.075), by multivariate analysis. These results support future studies on the role of rs887569 EZH2 SNP as a possible predictive marker of OS in advanced CCA patients.
authors.affiliation: Department of Internal Medicine, Division of Pharmacology, University of Pisa, Pisa I-56126, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Paolicchi
authors.forename: Paola
authors.initials: P
authors.lastname: Pacetti
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Mambrini
authors.forename: Massimo
authors.initials: M
authors.lastname: Orlandi
authors.forename: Francesco
authors.initials: F
authors.lastname: Crea
authors.forename: Antonello A
authors.initials: AA
authors.lastname: Romani
authors.forename: Roberta
authors.initials: R
authors.lastname: Tartarini
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cantore
keywords: ECX regimen; EZH2; cholangiocarcinoma; polycomb; polymorphism