Patients With Non-small Cell Lung Cancer Tissue Of Thymidylate Synthase Expression And Serum Levels Of Correlation Study

Background and objective: More than 80% patients are advanced stage when non-small cell lung cancer (NSCLC) is diagnosed and they misse the chance to be resected. Chemotherapy is one of the effective methods but only 20-40% patients can benefit from it with the median survival of 8-10 months. Parmacogenomics is different with variant histological types. Heterogenicity of effectiveness and toxicity can be found in different race and individual that many of the patients endure ineffective therapy and toxicity. As the study of tumor molecular biology advances, the differentiation of tumor gene pool conduct the individual chemotherapy is gradually recognized. According to specific molecular targets to select therapy are accepted extensively. The stageing system can not precisely predict the effect of the therapy to NSCLC , so research of biologic target to give different therapy to different histologic types is hot topic in dignose and therapy of lung cancer.Thymidylate synthase(TS)is reported to be the only source of cellular thymidine which play important role in the prosees of DNA copy and cell growth. Activity of thymidine in many tumor tissue are increased and it had been one of the effective target of chemotherapy. Preclinical trial reported【1】the level of TS activity affect the drug activity to tumor. TS level may be a predictive marker of TS inhibitor effect. But how to monitor TS level to guide and value clinical therapy still has not be definitely established. Although more research reported about intestinal tumor, still less reported about lung cancer. So this paper is to study serum TS concentration and tissue TS level, analyse the relation between them and the clinical charecterisms. The objective is to investigate whether serum TS concentration can reflect its tissue level and to offer an effective method to monitor TS in NSCLC patients. Methods: TS serum concentration and tissue expression were determined in 110 patients with NSCLC by ELISA (enzyme linked immunosorbent assay) and immunohistochemicalstaining respectively. And 34 healthy volunteers were determined TS serum concentration at the same time to be the base line. Correlation was analyzed between TS serum level and tissue expression.Results:(1).TS serum concentration of NSCLC patients was (68.89±67.69)pg/ml , while it was (23.15±17.08)pg/ml in the healthy. TS serum concentration was significantly increased in patients with NSCLC(P<0.05);(2).TS serum concentration was significantly higher in patients with higher TNM stage(P<0.05);(3).The patients with metastasized lymp node had higher TS serum leve(l88.88±103.47)pg/ml than those without metastasized lymp node(58.34±33.60)pg/ml(P<0.05);(4).65.50%(72/110)NSCLC patients'tumor tissue expressed TS;The positive expression of TS was related with tumor histologic type.It was espectively 79.20% and 56.40% in adenocarcinoma and squamous carcinoma(P<0.05);(5).The positive expression of TS was related with tumor differentiation (87.88% to 55.84%)(P<0.05);(6).With or without metastasized lymp node determined different TS expression in NSCLC tumor sissue(78.95% to 58.33%) (P<0.05);(7).Significantly correlation was found between TS serum concentration and tissue expression(P<0.05).Conclusions:(1).TS serum concentration was significantly increased in patients with NSCLC.(2).Tumor TNM stage and metastasized lymp node related to TS serum concentration. (3).65.50% of NSCLC tumor tissue expressed TS and correlated with histologic type, tumor differentiation and metastasized lymp node .(4).TS serum concentration was significantly correlated to tumor expression. TS serum concentration could reflect its tumor expression .