The Impact Of 5-Fluorouracil Metabolic Enzymes On The Response In Gastric Cancer Patients Treated With S-1:A Meta-Analysis

Objective:The predictive value of 5-fluorouracil metabolic enzymes for clinical sensitivity to S-1 chemotherapy in gastric cancer patients remains questioned. The objective of this meta-analysis is to provide an assessment of the relationship between the expression variations of 5-fluorouracil metabolic enzymes and clinical outcomes in patients with gastric cancer treated with S-1, including thymidylate synthase (TS), thymidine phosphorylase (TP), orotate phosphoribosyl transferase (OPRT) and dihydropyrimidine dehydrogenase (DPD). And we explore further the possibility of considering 5-fluorouracil metabolic enzymes as biomarkers to predict the efficacy of the S-1 treatment.Methods:Establishing searching strategies, inclusive criteria and exclusive criteria. Searching the databases PUBMED, EMBASE, CBM, CNKI, VIP electronically. References of retrieved articles and important meeting materials were also considered. Studies in gastric cancer patients treated with S-1 investigating the expression variations of 5-fluorouracil metabolic enzymes were included after identifying systematically (last search date:19, April 2015). A statistical analysis of the results were calculated by the Stata/SE 12.0 and Corhrane Collaboration’s Review Manager 5.3 softwares.Results:There were a total of 555 patients in ten studies that met our inclusion criteria. Nine literature have data of short-term effect. High/+expression of TS was found in 159 patients, and low/-expression of TS was found in 186 patients. High/+ expression of TP was found in 116 patients, and low/-expression of TP was found in 125 patients. High/+expression of OPRT was found in 179 patients, and low/-expression of OPRT was found in 106 patients. High/+expression of DPD was found in 155 patients, and low/-expression of DPD was found in 186 patients. There was a significant difference in the objective response rate between the patients with high/+ expression OPRT expression and the patients with low/-expression OPRT expression (OR= 8.06; 95%CI,4.06-16.02; p<0.001). And the objective response rate for S-1 chemotherapy was significantly higher in patients with high/+expression DPD than patients with low/-expression of DPD(OR= 1.95; 95% CI,1.21-3.13; p= 0.006).There was no significant difference in the objective response rate between in the expression of TP and TS. Four literature have data of short-term effect. High/+ expression of TS was found in 50 patients, and low/-expression of TS was found in 97 patients. High/+expression of TP was found in 51 patients, and low/-expression of TP was found in 56 patients. High/+expression of OPRT was found in 81 patients, and low/-expression of OPRT was found in 23 patients. High/+expression of DPD was found in 47 patients, and low/-expression of DPD was found in 131 patients. Although patients with TP(low/-),TS (low/-) and DPD(high/+) have a longer median overall survival time, all the difference was not statistically significant.There was a significant difference in median overall survival between the patients with high/+ expression OPRT expression and the patients with low/-expression OPRT expression (p=0.076).Conclusions:High/+expression of OPRT and DPD were associated with higher objective response in gastric cancer patients treated with S-1 chemotherapy. Meanwhile, high/+expression of OPRT was associated with longer median overall survival.OPRT and DPD expression in gastric carcinoma tissues may be suitable significant predictors of the efficacy of S-1 chemotherapy in patients with gastric cancer.