Abstract
BackgroundThe potential prognostic value of human equilibrative nucleoside transporter1 in pancreatic cancer receiving gemcitabine-based chemotherapy is variably reported.ObjectiveThe 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.MethodsRelated 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.ResultsA 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.ConclusionThese 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.
Highlights
Pancreatic carcinoma, one of the most lethal malignancies, is the fourth leading cause of cancer-related deaths worldwide [1], partly due to resistance to most chemotherapeutic drugs
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
Of the studies selected for detailed evaluation, 1 study was excluded as replicate [23] and 1 study was excluded due to missing hazard ratio (HR) data [24]
Summary
Pancreatic carcinoma, one of the most lethal malignancies, is the fourth leading cause of cancer-related deaths worldwide [1], partly due to resistance to most chemotherapeutic drugs. Gemcitabine (GEM), the nucleoside pyrimidine analogue, is approved for use in non–small-cell lung cancer, breast cancer, and ovarian cancer. It is one of the most commonly used chemotherapeutic agents and is the single most effective agent in the palliation of advanced pancreatic cancer, where it has been shown to improve clinical symptoms and modestly extend survival [4]. Efficient permeation of gemcitabine across cell membranes requires specialized integral membrane transporter proteins [9] Among these transporters, the human equilibrative nucleoside transporter 1(hENT1) is the major mediator of gemcitabine uptake into human cells [10]. The potential prognostic value of human equilibrative nucleoside transporter in pancreatic cancer receiving gemcitabine-based chemotherapy is variably reported
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