OPRT,DPYD,TS的mRNA水平与胃癌对氟尿嘧啶敏感性的相关性研究

Gene expression of fluorouracil metabolic enzymes in gastric cancer correlation with ex vivo chemosensitivity towards fluorouracil

目的:探讨胃癌细胞中乳清酸磷酸核糖转移酶(orotate phosphoribosyltransferase,OPRT)、二氢嘧啶脱氢酶(dihydropy-rimidine dehydrogenase,DPYD)、胸腺嘧啶合成酶(thymidylate synthase,TS)的表达水平对氟尿嘧啶药物敏感性的预测价值。方法:采用ATP生物荧光法检测47例胃癌原代细胞对氟尿嘧啶的体外药物敏感性,RT-PCR法检测胃癌细胞内OPRT、DPYD、TS的mRNA表达水平,并分析胃癌细胞对氟尿嘧啶体外敏感性与这3种酶表达的关系。结果:OPRT的mRNA表达水平为0.74±0.36,DPYD的mRNA表达水平为0.85±0.35,TS的mRNA表达水平为0.57±0.28。药敏指数与OPRTmRNA表达水平呈正相关(rs=0.744,P=0.001);与TSmRNA表达水平呈负相关(rs=-0.375,P=0.009);与DPYDmRNA表达水平呈负相关(rs=-0.159,P=0.287),但无统计学显著性。结论:胃癌细胞中OPRT和TSmRNA的表达水平对氟尿嘧啶药物的治疗敏感性可能具有较好的预测价值。

Objective：To investigate the potential role of orotate phosphoribosyltransferase （OPRT）,dihydropyrimidine dehydroge- nase（DPYD） and thymidylate synthase（TS） in serving as biomarkers for drug sensitivity in primary gastric cancer. Methods：Viable tumor cells obtained from the samples of forty-seven patients with gastric carcinoma were tested for their sensitivity to 5-fluorouracil using ATP-TCA assay. Reverse transcription-PCR was used to measure the mRNA level of the three 5-fluorouracil related genes. Results： OPRT mRNA level was positively correlated with the sensitivity to 5-fluorouracil （r=0.744,P=0.001） while TS mRNA level was negatively correlated with the sensitivity （r=-0.375,P=0.009）. No significant association was observed between DPYD expression and 5-fluorouracil sensitivity （r=-0.159,P=0.287）. Conclusion：Detection of the expression level of OPRT and TS mRNA in gastric cancer might be of good value for predicting the sensitivity to 5-fluorouracil.