Prognostic value of human equilibrative nucleoside transporter1 in pancreatic cancer receiving gemcitabin-based chemotherapy: a meta-analysis

PLoS One. 2014 Jan 27;9(1):e87103. doi: 10.1371/journal.pone.0087103. eCollection 2014.

Abstract

Background: The potential prognostic value of human equilibrative nucleoside transporter1 in pancreatic cancer receiving gemcitabine-based chemotherapy is variably reported.

Objective: The objective of this study was to conduct a systematic review of literature evaluating human equilibrative nucleoside transporter1 expression as a prognostic factor in pancreatic cancer receiving gemcitabine-based chemotherapy and to conduct a subsequent meta-analysis to quantify the overall prognostic effect.

Methods: Related studies were identified and evaluated for quality through multiple search strategies. Only studies analyzing pancreatic cancer receiving gemcitabine-based chemotherapy were eligible for inclusion. Data were collected from studies comparing overall, disease-free and progression-free survival (OS, DFS and PFS) in patients with low human equilibrative nucleoside transporter1 levels and those having high levels. The hazard ratio (HR) and its 95% confidence interval (95%CI) were used to assess the strength of associations. Hazard ratios greater than 1 reflect adverse survival associated with low human equilibrative nucleoside transporter1 levels.

Results: A total of 12 studies (n = 875) were involved in this meta-analysis (12 for OS, 5 for DFS, 3 for PFS). For overall and disease-free survival, the pooled HRs of human equilibrative nucleoside transporter1 were significant at 2.93 (95% confidence interval [95% CI], 2.37-3.64) and 2.67 (95% CI, 1.87-3.81), respectively. For progression-free survival, the pooled HR in higher human equilibrative nucleoside transporter1 expression in pancreatic cancer receiving gemcitabine-based chemotherapy was 2.76 (95% CI, 1.76-4.34). No evidence of significant heterogeneity or publication bias was seen in any of these studies.

Conclusion: These results support the case for a low human equilibrative nucleoside transporter1 level representing a significant and reproducible marker of adverse prognosis in pancreatic cancer receiving gemcitabine-based chemotherapy.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Equilibrative Nucleoside Transporter 1 / metabolism*
  • Humans
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism*
  • Prognosis
  • Proportional Hazards Models

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Equilibrative Nucleoside Transporter 1
  • SLC29A1 protein, human
  • Deoxycytidine
  • gemcitabine

Grant support

This article is supported by the National Natural Science Foundation of China (NO 30872591) and Shanghai Science and Technology Commission (NO: 11411950602). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.