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目的探讨胸苷酸合成酶(TS)、二氢嘧啶脱氢酶(DPD)和胸苷磷酸化酶(TP)在胃癌中的mRNA表达,及与临床病理特征和5-氟尿嘧啶(5-Fu)化疗敏感性的关系。方法应用半定量逆转录-聚合酶链反应(RT-RCR)检测了TS、DPD和TP mRNA在4株胃癌细胞、52例胃癌肿瘤和正常组织中的表达,比较了酶表达水平和临床病理特征之间的关系;噻唑蓝(MTT)法检测4株胃癌细胞的5-Fu半数抑制浓度(IC50),及30例标本的5-Fu体外药物敏感性,探讨其与氟尿嘧啶代谢酶mRNA水平的关系。结果4株胃癌细胞均阳性表达TS、DPD和TP mRNA,DPD mRNA水平与5-Fu IC50之间显著相关(r=0.999,P<0.01),TS mRNA或TP mRNA与5-Fu IC50之间无显著相关性(P>0.05)。肿瘤组织的TS和TP mRNA水平均显著高于邻近正常组织(1.32±0.70 vs 0.93±0.48,P<0.01;0.65±0.37 vs 0.51±0.33,P<0.01),DPD mRNA水平在肿瘤与正常组织间的差异无统计学意义(0.89±0.39 vs 0.93±0.47,P>0.05)。TS表达与浸润深度(P<0.05)、远处转移(P<0.01)和TNM分期(P<0.01)相关,DPD在肠型胃癌中的表达显著高于弥漫型(P<0.01),且倾向高表达于肿瘤面积<5cm者(P<0.01),TP mRNA表达与浸润深度(P<0.05)和远处转移(P<0.05)有关。TS mRNA(r=-0.540,P<0.01)及DPD mRNA水平(r=-0.672,P<0.01)与5-Fu敏感性负相关,TP水平与5-Fu敏感性无显著相关(r=-0.317,P>0.05)。结论胃癌肿瘤内TS和TP mRNA表达显著高于正常组织,且与胃癌分期关系密切,DPD mRNA与Laurén分型和肿瘤面积有关,细胞试验和原代培养均提示DPD mRNA低水平表达可能是5-Fu高敏感性的预测指标。
Objective To investigate the mRNA expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) in gastric carcinoma and its relationship with clinicopathological features and 5-fluorouracil Chemosensitivity relationship. Methods The expressions of TS, DPD and TP mRNA in 4 gastric cancer cell lines, 52 gastric cancer tissues and normal tissues were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-RCR). The enzyme expression level and clinicopathological features were compared The IC50 values of 5-Fu in 4 gastric cancer cells and the 5-Fu drug sensitivity in 30 specimens were determined by MTT assay and the relationship between 5-Fu and 5-Fu mRNA level . Results TS, DPD and TP mRNA were positively expressed in all the four gastric cancer cell lines, and DPD mRNA level was significantly correlated with 5-Fu IC50 (r = 0.999, P <0.01). There was no significant difference between TS mRNA, TP mRNA and 5-Fu IC50 Significant correlation (P> 0.05). The levels of TS and TP mRNA in tumor tissue were significantly higher than those in adjacent normal tissues (1.32 ± 0.70 vs 0.93 ± 0.48, P <0.01; 0.65 ± 0.37 vs 0.51 ± 0.33, P <0.01) The difference was not statistically significant (0.89 ± 0.39 vs 0.93 ± 0.47, P> 0.05). The expression of TS was correlated with the depth of invasion (P <0.05), distant metastasis (P <0.01) and TNM stage (P <0.01). The expression of TSD in intestinal type gastric cancer was significantly higher than that in diffuse type The expression of TP mRNA was correlated with the depth of invasion (P <0.05) and distant metastasis (P <0.05). There was a negative correlation between TS mRNA (r = -0.540, P <0.01) and DPD mRNA (r = -0.672, P <0.01) and 5-Fu sensitivity 0.317, P> 0.05). Conclusions The expressions of TS and TP mRNA in gastric cancer tissues are significantly higher than those in normal tissues and closely related to gastric cancer staging. The DPD mRNA is related to Laurén classification and tumor size. Both cell culture and primary culture suggest that DPD mRNA expression may be low in 5- Fu high sensitivity prediction index.