A polymorphism in the promoter is associated with EZH2 expression but not with outcome in advanced pancreatic cancer patients

Pharmacogenomics. 2014 Apr;15(5):609-18. doi: 10.2217/pgs.13.225.

Abstract

Aim: EZH2 expression is a prognostic marker in radically resected pancreatic ductal adenocarcinoma (PDAC) patients. Here we investigated its role in locally advanced/metastatic patients, as well as candidate polymorphisms.

Materials & methods: EZH2 expression and polymorphisms were evaluated by quantitative reverse transcription PCR in 32 laser microdissected tumors, while polymorphisms were also studied in blood samples from two additional cohorts treated with gemcitabine monotherapy (n = 93) or polychemotherapeutic regimens (n = 247).

Results: EZH2 expression correlated with survival and with the rs6958683 polymorphism in the first cohort of patients, but this polymorphism was not associated with survival in our larger cohorts.

Conclusion: EZH2 is a prognostic factor for locally advanced/metastatic PDACs, while candidate polymorphisms cannot predict clinical outcome. Other factors involved in EZH2 regulation, such as miR-101, should be investigated in accessible samples in order to improve the clinical management of advanced PDAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use
  • Cohort Studies
  • DNA / genetics
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Disease Progression
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Gemcitabine
  • Humans
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology*
  • Polycomb Repressive Complex 2 / genetics*
  • Polymorphism, Genetic / genetics
  • Promoter Regions, Genetic / genetics
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • MIRN101 microRNA, human
  • MicroRNAs
  • Deoxycytidine
  • DNA
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • Gemcitabine