Ishida Hideyuki, Shirakawa Kazuo, Ohsawa Tomonori, Sobajima Jun, Hayashi Yoichi, Nakada Hiroshi, Yokoyama Masaru, Hashimoto Daijo
Dept. of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical School.
Gan To Kagaku Ryoho. 2005 Nov;32(12):1929-34.
We semiquantificated the mRNA levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase(OPRT) from the frozen tissue of colorectal cancer, in order to examine the relationships among these enzymes and the efficacy for 5-fluorouracil (FU)-based treatment in terms of the combinations of the expression levels of these enzymes. There were weak and positive relationships among TS mRNA expression and OPRT mRNA expression or DPD mRNA expression, while there was no significant relationship between DPD mRNA expression and OPRT mRNA expression (n = 112). In 39 patients who received 5-FU-based chemotherapy with evaluable lesions, patients with low TS expression (n = 23) showed a higher response rate (52%) as compared to those with high TS expression (13%, p = 0.02). Patients with low TS, low DPD, or high DPD expression tended to show a higher response rate (50%) than those with the other combinations (26%, p = 0.09). In addition, all of the responders with only one favorable factor (n = 4) were associated with low TS or low DPD expression. In conclusion, low TS expression followed by low DPD expression is important to predict the efficacy of 5-FU-based treatment for colorectal cancer. However, it may be of little significance to semiquantify the expression of OPRT.
我们对结直肠癌冷冻组织中的胸苷酸合成酶(TS)、二氢嘧啶脱氢酶(DPD)和乳清酸磷酸核糖转移酶(OPRT)的mRNA水平进行了半定量分析,以研究这些酶之间的关系,以及基于这些酶表达水平组合的5-氟尿嘧啶(FU)治疗效果。TS mRNA表达与OPRT mRNA表达或DPD mRNA表达之间存在微弱的正相关关系,而DPD mRNA表达与OPRT mRNA表达之间无显著相关性(n = 112)。在39例接受基于5-FU化疗且有可评估病灶的患者中,TS低表达患者(n = 23)的缓解率(52%)高于TS高表达患者(13%,p = 0.02)。TS低表达、DPD低表达或DPD高表达的患者缓解率(50%)往往高于其他组合的患者(26%,p = 0.09)。此外,所有仅有一个有利因素的缓解者(n = 4)均与TS低表达或DPD低表达相关。总之,TS低表达继而DPD低表达对于预测基于5-FU的结直肠癌治疗疗效很重要。然而,对OPRT表达进行半定量分析可能意义不大。