Thymidine phosphorylase mRNA level predicts survival of patients with advanced oropharyngeal cancer.
CONCLUSIONS
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.


BACKGROUND
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.


METHODS
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.


RESULTS
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).
Ijuin
Takahiro
T
Department of Otolaryngology-Head and Neck Surgery, Kobe University Hospital, Kobe, Japan.
Nibu
Ken-ichi
K
Doi
Kiyoshi
K
Inoue
Hiroyuki
H
Saitoh
Miki
M
Ohtsuki
Naoki
N
Makino
Kunihiko
K
Amatsu
Mutsuo
M
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D013223:Statistics as Topic; D013939:Thymidine Phosphorylase / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil