Study On The Correlation Between TSER Polymorphism And Sensitivity Of Gastric Cancer Tissue To 5-Fluorouracil In Vitro

PURPOSE:Chemotherapy possess an impotant status in the all-around therapy of gastric cancer as operation.But there is no pertinence in current experiential chemotherapy. In the recent years,the study that the chemosensitivity assay guilds clinical individual chemotherapy is attached importance to by doctors.Vitro drug sensitivity assay which applies on human fresh tissue is good for applying drug, foreasting drug sensiyivity to individual tumor cells,instructing clinic,improving curative effect. But there are some disadvantages.Firstly,experimental period is too long. Secondly,experimental operations are hard.Finally,it is difficult to acquire the samples.Therefore,it is an exigent task to find out a kind of test to replace chemosensitivity test. We have to analyse the relationship between the TSER polymorphism and vitro chemosensitivity test and evaluate whether TSER genotype test can replace the chemosensitivity test of tumor cells in vitro to guide clinical individual chemotherapy. The study will be helpful in the clinical individual chemotherapy of gastric cancer.(1) To investigate the relativity between TSER Polymorphism and sensitivity of gastric cancer tissue to 5-Fluorouracil in vitro.(2) To investigate the relationship of the TS expression level with TSER Polymorphism and sensitivity of gastric cancer tissue to 5-Fluorouracil in vitro.METHODS:(1) The gastric carcinoma cells taken from fresh samples of 45 patients were cultured in vitro to test the sensitivity of these cells to 5-Fu with the method of ATP-TCA.TSER genotypes were detected by PCR method,and the correlation between outcome of the genotyping of TSER polymorphisms and chemosensitivity assay was then compared .(2)The expression level of TS in 35 gastric cancer tissues out of the 45 was detected by means of immunohistochemistry。 RESULTS:(1) The overall response rate to 5-Fu was 33.3%(14/42).The response rate of 2R/2R and 2R/3R genotype group to 5-Fu was56.3﹪(9/16) and was higher than that of 3R / 3R genotype group ( 19.2﹪, 5/26). The incidence rates of chemosensitivity assay in gastric cancer tissue were significantly different between 2R/2R,2R/3R and 3R/3R genotype groups(P=0.017)。(2)The high-level expression rate of type 3R/3R was 61.9%(13/21),which was higher than that of type 2R/2R and 2R/3R (21.4%,3/14)(P=0.021)。The response rate of the low-level TS group to 5-Fu was 52.9﹪(9/17)and was significantly higher than that of the high-level TS group(18.8﹪,3/16,P=0.046)。CONCLUSIONS:(1) The results in the present study suggest that the polymorphism of TSER is associated with the antitumor activities of 5-fluorouracil, indicating that the genotyping of TSER polymorphisms might be used as stratification maker for predicting the antitumor activities of 5-fluorouracil. Genotyping the tandem repeat sequences of TSER is useful for individualized therapy involving fluoropyrimidine antitumor drugs.(2) The results in the present study suggest that The TSER polymorphism is probably associated with the antitumor activities of 5-fluorouracil under the dependence of TS expression levels.The TSER polymorphism may influence the TS mRNA level.TS expression levels may affect chemotherapy.