From the *Division of General Surgery, Department of Surgery, †Department of Statistics, ‡Jonsson Comprehensive Cancer Center, §Department of Medicine, Division of Digestive Disease, ∥Institute for Molecular Medicine, and ¶Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.
Pancreas. 2013 Nov;42(8):1303-10. doi: 10.1097/MPA.0b013e3182a23ae4.
The objective of this study was to summarize all clinical studies evaluating the prognostic role of gemcitabine (GEM) metabolic genes in pancreaticobiliary (PB) cancer patients receiving GEM therapy in the neoadjuvant, adjuvant, or palliative settings.
Meta-analyses were performed to calculate the pooled hazard ratios for each gene by each clinical outcome (overall survival [OS], disease-free survival [DFS], and progression-free survival) using a random-effects approach.
The search strategy identified 16 eligible studies, composed of 632 PB patients total, with moderate quality. Compared with low expression, pooled hazard ratios for OS of hENT1, dCK, RRM1, RRM2, and DPD were 0.37 (95% confidence interval [CI], 0.28-0.47), 0.40 (95% CI, 0.20-0.80), 2.21 (95% CI, 1.12-4.36), 2.13 (95% CI, 1.00-4.52), and 1.91 (95% CI, 1.16-3.17), respectively. A similar trend was observed for each of these biomarkers in DFS and progression-free survival prognostication. Subgroup analyses for hENT1 showed a comparable survival correlation in the adjuvant and palliative settings.
High expression of hENT1 in PB cancer patients receiving GEM-based adjuvant therapy is associated with improved OS and DFS and may be the best examined prognostic marker to date. Evidence for other biomarkers is limited by a small number of publications investigating these markers.
本研究旨在总结所有评估吉西他滨（GEM）代谢基因在接受 GEM 治疗的胰胆管（PB）癌患者中的预后作用的临床研究，这些患者的治疗方案包括新辅助治疗、辅助治疗或姑息治疗。
采用随机效应方法，通过每个基因的每个临床结局（总生存[OS]、无病生存[DFS]和无进展生存）进行荟萃分析，计算每个基因的合并风险比。
搜索策略确定了 16 项符合条件的研究，共纳入 632 名 PB 患者，这些研究的质量为中等。与低表达相比，hENT1、dCK、RRM1、RRM2 和 DPD 的 OS 汇总风险比分别为 0.37（95%置信区间[CI]，0.28-0.47）、0.40（95% CI，0.20-0.80）、2.21（95% CI，1.12-4.36）、2.13（95% CI，1.00-4.52）和 1.91（95% CI，1.16-3.17）。在 DFS 和无进展生存预测中，这些生物标志物也观察到了类似的趋势。hENT1 的亚组分析表明，在辅助治疗和姑息治疗中，其生存相关性相当。
在接受吉西他滨为基础的辅助治疗的 PB 癌患者中，hENT1 高表达与 OS 和 DFS 改善相关，可能是迄今为止最佳的检查预后标志物。其他生物标志物的证据受到调查这些标志物的出版物数量较少的限制。
