A predictive factor for the response to S-1 plus cisplatin in gastric cancer

AIM:To prove that the protein expression level of thymidylate synthase is a predictive factor for the response to S-1/cisplatin(CDDP)chemotherapy in gastric cancer.METHODS:We measured the protein expression levels of thymidylate synthase(TS),dihydropyrimidine dehydrogenase(DPD),and orotate phosphoribosyltrans-ferase(OPRT)in advanced gastric cancer.Before S-1/CDDP chemotherapy,tumor specimens from primary sites were obtained by endoscopic biopsy and analyzed by enzyme-linked immunosorbent assay.The chemo-therapeutic effects on the primary sites were evaluated by endoscopic biopsy performed more than once after S-1/CDDP chemotherapy.The effects are a predictive factor for the response to S-1/CDDP chemotherapy inpatients with advanced gastric cancer,as evaluated by endoscopic biopsy over time.RESULTS:The protein expression level of TS was significantly higher(P<0.05)in the tumor than in the normal tissue,and significantly lower(P<0.05)in the responders than in the non-responders.We were able to evaluate the correlation between changes in the protein expression levels of TS,DPD and OPRT and chemotherapeutic responses in 7 patients by assessing tumor tissues more than twice.In the responders,the protein expression level of TS was<40 ng/mg protein.However,there were significant increases in the protein expression levels of TS(P<0.01)and DPD(P<0.05)after chemotherapy in 3 patients.In these cases,the patient assessment changed from"responder"to"non-responder".In the non-responders,the protein expression level of TS was>40 ng/mg protein.CONCLUSION:We have confirmed that the protein expression level of TS is a predictive factor for the response to S-1/CDDP chemotherapy in patients with advanced gastric cancer.