Prognostic Implications of Expression Profiling for Gemcitabine-Related Genes (hENT1, dCK, RRM1, RRM2) in Patients With Resectable Pancreatic Adenocarcinoma Receiving Adjuvant Chemotherapy

Pancreas. 2017 May/Jun;46(5):684-689. doi: 10.1097/MPA.0000000000000807.

Abstract

Objectives: The aim of this study was to examine the relevance of expression profiling of 4 genes involved in the action of gemcitabine among patients with pancreatic ductal-cell adenocarcinoma (PDAC).

Methods: A group of 100 patients who underwent pancreatic resections for PDAC and received adjuvant chemotherapy with gemcitabine between 2007 and 2010 was identified. Expression of mRNAs for human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunits (RRM1, RRM2), and deoxycytidine kinase (dCK) was examined by quantitative real-time polymerase chain reaction, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and dichotomized into groups of low and moderate/high expression levels grouped by tertiles.

Results: Significantly better median survival times were found for high/moderate expression levels of hENT1 (27.9 vs 12.4 months, P = 0.001) and dCK (19.7 vs 10.5 months, P = 0.003), as well as low expression of RRM1 (23.4 vs 11.4 months, P = 0.027). A Cox proportional hazards model identified low expression of hENT1 (hazard ratio [HR], 3.38; 95% confidence intervals [CI], 2.28-10.50) and dCK (HR, 2.24; 95% CI, 1.63-3.39), and high/moderate levels of RRM1 (HR, 1.65; 95% CI, 1.23-2.45) as negative prognostic factors.

Conclusions: Expression of hENT, RRM1, and dCK genes provides important prognostic information for PDAC patients treated with adjuvant gemcitabine.

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / surgery
  • Chemotherapy, Adjuvant
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Deoxycytidine Kinase / genetics
  • Equilibrative Nucleoside Transporter 1 / genetics
  • Female
  • Gemcitabine
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Ribonucleoside Diphosphate Reductase / genetics
  • Tumor Suppressor Proteins / genetics

Substances

  • Antimetabolites, Antineoplastic
  • Equilibrative Nucleoside Transporter 1
  • SLC29A1 protein, human
  • Tumor Suppressor Proteins
  • Deoxycytidine
  • ribonucleotide reductase M2
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • Deoxycytidine Kinase
  • Gemcitabine