Mauritz Robert, van Groeningen Cees J, Smid Kees, Jansen Gerrit, Pinedo Herbert M, Peters Godefridus J
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Int J Cancer. 2007 Jun 15;120(12):2609-12. doi: 10.1002/ijc.22626.
This study explores the effect of 5-fluorouracil (5FU) exposure on mRNA levels of its target enzyme thymidylate synthase (TS) and the rate-limiting catabolic enzyme dihydropyrimidine dehydrogenase (DPD) in tumors of colorectal cancer patients. TS and DPD mRNA levels were determined in primary tumor and liver metastasis samples from patients who were either not pretreated (n = 29) or given one presurgery bolus of 5FU (n = 67). In both groups a wide variation in TS mRNA levels was observed. Median TS mRNA expression in 17 primary tumors of exposed patients was 3.0-fold higher than in 19 primary tumors of unexposed patients (p = 0.015). TS mRNA expression in liver metastasis samples of exposed patients (n = 16) was also higher (5.2-fold) than that of unexposed patients (n = 48; p < 0.001). Also DPD mRNA expression displayed a large degree of interpatient variation. No difference in DPD expression in liver metastasis samples was observed between exposed and unexposed patients. However, median DPD mRNA expression in 15 primary tumors of exposed patients was 3.2-fold lower than in 18 primary tumors of unexposed patients (p = 0.027). In conclusion, administration of 5FU in vivo influences the gene expression of TS and DPD.
本研究探讨了5-氟尿嘧啶（5FU）暴露对结直肠癌患者肿瘤中其靶酶胸苷酸合成酶（TS）和限速分解代谢酶二氢嘧啶脱氢酶（DPD）mRNA水平的影响。在未接受预处理的患者（n = 29）或接受一次术前5FU推注的患者（n =
67）的原发性肿瘤和肝转移样本中测定TS和DPD mRNA水平。在两组中均观察到TS mRNA水平存在广泛差异。暴露患者的17个原发性肿瘤中TS mRNA的中位表达比未暴露患者的19个原发性肿瘤高3.0倍（p = 0.015）。暴露患者（n =
16）肝转移样本中的TS mRNA表达也高于未暴露患者（n = 48；p < 0.001），高5.2倍。DPD mRNA表达也显示出患者间的较大差异。在暴露和未暴露患者的肝转移样本中未观察到DPD表达的差异。然而，暴露患者的15个原发性肿瘤中DPD mRNA的中位表达比未暴露患者的18个原发性肿瘤低3.2倍（p = 0.027）。总之，体内给予5FU会影响TS和DPD的基因表达。
