Abstract
The potential impact that the intratumoral expression level of dihydropyrimidine dehydrogenase (DPD) has on chemotherapy sensitivity and long-term survival for gastric cancer (GC) patients remains controversial; therefore, this study seeks to clarify this issue. Our meta-analysis was performed using Review Manager (RevMan) 5.3 software. In vitro drug sensitivity tests, correlation coefficients between sensitivity to 5-fluorouracil (5-FU), and expression levels of intratumoral DPD were used as effective indexes to analyse. Overall survival (OS) and progression-free survival (PFS) were used as endpoints for patient outcome, and hazard ratios (HRs) and 95% confidence intervals (CIs) were noted as measures of effect. There were 15 eligible studies including 1805 patients for the final analysis. The analysis revealed a statistically significant difference between the expression level of intratumoral DPD activity, DPD mRNA levels, and sensitivity to 5-FU in GC patients, with high expression levels of intratumoral DPD resulting in low sensitivity to 5-FU. However, no matter what therapeutic regimens were used, there was no significant difference for patient outcomes between high and low DPD expression groups, either in OS or in PFS. In conclusion, high levels of intratumoral DPD expression have a negative impact on sensitivity to 5-FU in GC patients, but no prognostic value for long-term survival was uncovered.
Highlights
The fourth most common malignant tumor type, gastric cancer (GC), is the second leading cause of cancer-related deaths worldwide [1, 2]
With the development of biomarker research, finding highly sensitive and specific biomarkers is becoming more important and popular [21,22,23]. In this meta-analysis, we focus on the relationship between expression levels of intratumoral dihydropyrimidine dehydrogenase (DPD) and sensitivity to 5-FU and outcome of GC patients, with the intent to establish the value of DPD as a biomarker
The results indicated that high expression levels of DPD in tumor tissue trended toward a negative impact on GC patient outcome, it was not statistically significance
Summary
The fourth most common malignant tumor type, gastric cancer (GC), is the second leading cause of cancer-related deaths worldwide [1, 2]. D2 radical resection is the standard treatment for advanced gastric cancer (AGC) patients; there is still no standard effective chemotherapy regimen for AGC [4,5,6]. Fluorouracil-based chemotherapy regimens have been widely used as first-line treatments for GC patients [7, 8]. 5-FU and S-1 are the most widely used fluorouracil and there are some differences between their components and pharmacological effects. Due to the significant heterogeneity in GC, there are wide discrepancies in the effect of the same fluorouracil-based regimens between patients [10, 11]. It is important to seek a biomarker to evaluate which patients will most benefit from fluorouracilbased regimens and to estimate the long-term outcome of GC patients
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