Ijuin Takahiro, Nibu Ken-ichi, Doi Kiyoshi, Inoue Hiroyuki, Saitoh Miki, Ohtsuki Naoki, Makino Kunihiko, Amatsu Mutsuo
Department of Otolaryngology-Head and Neck Surgery, Kobe University Hospital, Kobe, Japan.
Acta Otolaryngol. 2007 Mar;127(3):305-11. doi: 10.1080/00016480600801381.
The present study suggested that a high level of thymidine phosphorylase (TP) gene expression is significantly associated with favorable prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. Further studies consisting of large series should be performed to confirm our present results.
Expression levels of the thymidylate synthase (TS) and 5-FU metabolic enzymes including dihydropyrimidine dehydrogenase (DPD), TP, and orotate phosphoribosyl transferase (OPRT), are reported to be associated with sensitivity to 5-FU-based chemotherapy in several cancers.
Intratumoral mRNA expression levels of TS, DPD, TP, and OPRT in pretreatment biopsy specimens were quantified in 27 patients with advanced oropharyngeal squamous cell carcinomas. Association of these expression levels with response to platinum and 5-FU-based chemotherapy and survival were analyzed statistically.
By Spearman's correlation analysis, significant correlation was observed between TS and TP (gamma=0.51, p=0.018). While no correlation was observed between the tumor regression and expression of any of the genes investigated, significant association was observed between prognosis and mRNA expression levels of TS and TP. Multivariate Cox regression analysis revealed that TP mRNA expression level is a significant factor predicting prognosis (hazard ratio (HR) = - 0.204, p=0.043).
本研究表明，胸苷磷酸化酶（TP）基因的高表达水平与接受基于5-氟尿嘧啶（5-FU）的化疗患者的良好预后显著相关。应开展包含大量病例的进一步研究以证实我们目前的结果。
据报道，胸苷酸合成酶（TS）以及5-FU代谢酶，包括二氢嘧啶脱氢酶（DPD）、TP和乳清酸磷酸核糖基转移酶（OPRT）的表达水平与几种癌症中基于5-FU的化疗敏感性相关。
对27例晚期口咽鳞状细胞癌患者预处理活检标本中TS、DPD、TP和OPRT的瘤内mRNA表达水平进行定量分析。对这些表达水平与铂类和基于5-FU的化疗反应及生存情况的相关性进行统计学分析。
通过Spearman相关性分析，观察到TS与TP之间存在显著相关性（γ = 0.51，p = 0.018）。虽然未观察到肿瘤消退与所研究的任何基因表达之间存在相关性，但观察到预后与TS和TP的mRNA表达水平之间存在显著关联。多因素Cox回归分析显示，TP mRNA表达水平是预测预后的一个显著因素（风险比（HR）= - 0.204，p = 0.043）。
