TP与DPD在胃癌组织中的表达及其意义

The Expression and Significance of Thymidine Phosphorylase and Dihydropyrimidine Dehydrogenase in Gastric Carcinoma

目的:探讨TP和DPD在胃癌中的表达,及其与临床病理特征和5-FU药物敏感性的关系。方法:应用ELISA法检测TP和DPD在52例胃癌肿瘤和正常组织中的表达,比较酶含量与临床特征间的关系,并对其中30例以MTT法测定5-FU敏感性,探讨其与TP、DPD水平的关系。结果:胃癌组织的TP和DPD蛋白含量均显著高于邻近正常组织(65.82±31.90vs.17.47±12.26U/mgprotein,P<0.001;24.48±10.87vs.11.89±4.35U/mgprotein,P<0.001)。TP表达与淋巴结转移(P=0.028)、TNM分期(P=0.019)和分化程度(P=0.033)相关;DPD在肠型胃癌中的表达显著高于弥漫型(P=0.001)。DPD蛋白水平与5-FU敏感性负相关(rs=0.426,P=0.019),TP水平与5-FU敏感性无显著相关性(rs=0.179,P=0.344)。结论:胃癌肿瘤内TP和DPD表达明显高于正常组织。TP与胃癌分期关系密切;DPD与Laurén分型有关,其在肠型胃癌中的表达显著高于弥漫型;DPD低水平表达可用作5-FU高敏感性的预测指标。

Objective： To assess the expression of thymidine phosphorylase （TP） and dihydropyrimidine dehydrogenase （DPD） in gastric carcinoma and to determine the correlation with the clinicopathologic features and chemosensitivity of 5-fluorouracil （5-FU）. Methods： ELISA was used to detect expression of the TP and DPD proteins in tumor tissue and adjacent normal tissue of 52 patients with gastric carcinoma. The relationship between the TP and DPD protein levels and clinicopathological features of gastric cancer was analyzed. MTT assay was employed to evaluate the 5-FU sensitivity of gastric cancer cells in vitro and this data was used to investigate the correlation between TP and DPD levels and sensitivity to 5-FU. Results： In gastric cancer, both TP and DPD protein levels were significantly higher compared to the normal paraneoplastic tissues （TP： 65.82±31.90 vs. 17.47±12.26 U/mg protein, P〈0.001; DPD： 24.48±10.87 vs. 11.89±4.35 U/mg protein, P〈0.001）. The expression of TP protein showed a positive correlation with lymph node metastasis （P=0.028）, TNM staging （P=0.019） and pathologic differentiation （P=0.033）, whereas the DPD protein tended to be highly expressed only in intestinal gastric cancer （P=0.001） compared to the asystematic type. DPD expression was inversely associated with 5-FU sensitivity （rs=0.426, P=0.019）, but no significant correlation was found between TP expression and 5-FU sensitivity （rs=0.179, P=0.344）. Conclusion： TP and DPD protein expression in tumor tissues is significantly higher than levels found in normal paraneoplastic tissues. There is a close correlation between TP expression and clinical staging of gastric cancer, and between DPD expression and Laurén grouping with the intestinal-type gastric cancer. A low level of DPD expression may be used as a predictor for 5-FU chemosensitivity.